A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Cause of Death
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).
Protection from an infectious disease agent that is mediated by B- and T- LYMPHOCYTES following exposure to specific antigen, and characterized by IMMUNOLOGIC MEMORY. It can result from either previous infection with that agent or vaccination (IMMUNITY, ACTIVE), or transfer of antibody or lymphocytes from an immune donor (IMMUNIZATION, PASSIVE).
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
Fas Ligand Protein
A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.
Nonsusceptibility to the pathogenic effects of foreign microorganisms or antigenic substances as a result of antibody secretions of the mucous membranes. Mucosal epithelia in the gastrointestinal, respiratory, and reproductive tracts produce a form of IgA (IMMUNOGLOBULIN A, SECRETORY) that serves to protect these ports of entry into the body.
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.
Amino Acid Sequence
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
The process by which antigen is presented to lymphocytes in a form they can recognize. This is performed by antigen presenting cells (APCs). Some antigens require processing before they can be recognized. Antigen processing consists of ingestion and partial digestion of the antigen by the APC, followed by presentation of fragments on the cell surface. (From Rosen et al., Dictionary of Immunology, 1989)
Subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2, gamma-interferon, and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, Th1 cells are associated with vigorous delayed-type hypersensitivity reactions.
Proto-Oncogene Proteins c-bcl-2
Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.
Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.
Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.
Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)
Recombinant DNA vectors encoding antigens administered for the prevention or treatment of disease. The host cells take up the DNA, express the antigen, and present it to the immune system in a manner similar to that which would occur during natural infection. This induces humoral and cellular immune responses against the encoded antigens. The vector is called naked DNA because there is no need for complex formulations or delivery agents; the plasmid is injected in saline or other buffers.
Disease Models, Animal
Tumor Cells, Cultured
In Situ Nick-End Labeling
An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.
Lymphocytic choriomeningitis virus
The type species of ARENAVIRUS, part of the Old World Arenaviruses (ARENAVIRUSES, OLD WORLD), producing a silent infection in house and laboratory mice. In humans, infection with LCMV can be inapparent, or can present with an influenza-like illness, a benign aseptic meningitis, or a severe meningoencephalomyelitis. The virus can also infect monkeys, dogs, field mice, guinea pigs, and hamsters, the latter an epidemiologically important host.
Killer Cells, Natural
Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.
Reactive Oxygen Species
Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.
Death, Sudden, Cardiac
Unexpected rapid natural death due to cardiovascular collapse within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as CHEST PAIN and CARDIAC ARRHYTHMIAS, particularly VENTRICULAR TACHYCARDIA, can lead to the loss of consciousness and cardiac arrest followed by biological death. (from Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed., 2005)
Apoptosis Regulatory Proteins
Tumor Necrosis Factor-alpha
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
bcl-2-Associated X Protein
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions.
Gene Expression Regulation
TNF-Related Apoptosis-Inducing Ligand
A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
A family of pattern recognition receptors characterized by an extracellular leucine-rich domain and a cytoplasmic domain that share homology with the INTERLEUKIN 1 RECEPTOR and the DROSOPHILA toll protein. Following pathogen recognition, toll-like receptors recruit and activate a variety of SIGNAL TRANSDUCING ADAPTOR PROTEINS.
Receptors, Antigen, T-Cell
Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
A state of prolonged irreversible cessation of all brain activity, including lower brain stem function with the complete absence of voluntary movements, responses to stimuli, brain stem reflexes, and spontaneous respirations. Reversible conditions which mimic this clinical state (e.g., sedative overdose, hypothermia, etc.) are excluded prior to making the determination of brain death. (From Adams et al., Principles of Neurology, 6th ed, pp348-9)
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
A long pro-domain caspase that contains a death effector domain in its pro-domain region. Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS.
V-Set Domain-Containing T-Cell Activation Inhibitor 1
A form of meningitis caused by LYMPHOCYTIC CHORIOMENINGITIS VIRUS. MICE and other rodents serve as the natural hosts, and infection in humans usually occurs through inhalation or ingestion of infectious particles. Clinical manifestations include an influenza-like syndrome followed by stiff neck, alterations of mentation, ATAXIA, and incontinence. Maternal infections may result in fetal malformations and injury, including neonatal HYDROCEPHALUS, aqueductal stenosis, CHORIORETINITIS, and MICROCEPHALY. (From Joynt, Clinical Neurology, 1996, Ch26, pp1-3)
Amino Acid Chloromethyl Ketones
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.
Dose-Response Relationship, Drug
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Protein Structure, Tertiary
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-12 is a 70 kDa protein that is composed of covalently linked 40 kDa and 35 kDa subunits. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells and plays a role in the stimulation of INTERFERON-GAMMA production by T-LYMPHOCYTES and NATURAL KILLER CELLS.
Enzyme-Linked Immunosorbent Assay
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
Cytotoxicity Tests, Immunologic
A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CTLA-4 ANTIGEN with high specificity and to CD28 ANTIGEN with low specificity. The interaction of CD80 with CD28 ANTIGEN provides a costimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.
A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 9 is activated during cell stress by mitochondria-derived proapoptotic factors and by CARD SIGNALING ADAPTOR PROTEINS such as APOPTOTIC PROTEASE-ACTIVATING FACTOR 1. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.
Cysteine Proteinase Inhibitors
Pore Forming Cytotoxic Proteins
Proteins secreted from an organism which form membrane-spanning pores in target cells to destroy them. This is in contrast to PORINS and MEMBRANE TRANSPORT PROTEINS that function within the synthesizing organism and COMPLEMENT immune proteins. These pore forming cytotoxic proteins are a form of primitive cellular defense which are also found in human LYMPHOCYTES.
The ability of tumors to evade destruction by the IMMUNE SYSTEM. Theories concerning possible mechanisms by which this takes place involve both cellular immunity (IMMUNITY, CELLULAR) and humoral immunity (ANTIBODY FORMATION), and also costimulatory pathways related to CD28 antigens (ANTIGENS, CD28) and CD80 antigens (ANTIGENS, CD80).
Reverse Transcriptase Polymerase Chain Reaction
A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)
RNA, Small Interfering
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Histocompatibility Antigens Class I
Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.
The non-susceptibility to infection of a large group of individuals in a population. A variety of factors can be responsible for herd immunity and this gives rise to the different definitions used in the literature. Most commonly, herd immunity refers to the case when, if most of the population is immune, infection of a single individual will not cause an epidemic. Also, in such immunized populations, susceptible individuals are not likely to become infected. Herd immunity can also refer to the case when unprotected individuals fail to contract a disease because the infecting organism has been banished from the population.
Recombinant Fusion Proteins
A cytokine produced by a variety of cell types, including T-LYMPHOCYTES; MONOCYTES; DENDRITIC CELLS; and EPITHELIAL CELLS that exerts a variety of effects on immunoregulation and INFLAMMATION. Interleukin-10 combines with itself to form a homodimeric molecule that is the biologically active form of the protein.
Receptors, Death Domain
A family of cell surface receptors that signal via a conserved domain that extends into the cell CYTOPLASM. The conserved domain is referred to as a death domain due to the fact that many of these receptors are involved in signaling APOPTOSIS. Several DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic mediators such as CASPASES.
Attitude to Death
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
Tumor Suppressor Protein p53
Membrane Potential, Mitochondrial
Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
Receptors, Tumor Necrosis Factor
Apoptosis Inducing Factor
A flavoprotein that functions as a powerful antioxidant in the MITOCHONDRIA and promotes APOPTOSIS when released from the mitochondria. In mammalian cells AIF is released in response to pro-apoptotic protein members of the bcl-2 protein family. It translocates to the CELL NUCLEUS and binds DNA to stimulate CASPASE-independent CHROMATIN condensation.
Receptors, TNF-Related Apoptosis-Inducing Ligand
Tumor necrosis factor receptor family members that are widely expressed and play a role in regulation of peripheral immune responses and APOPTOSIS. The receptors are specific for TNF-RELATED APOPTOSIS-INDUCING LIGAND and signal via conserved death domains that associate with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
Receptors, Cell Surface
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Programmed cell death protein 1
"PD-L1 co-stimulation contributes to ligand-induced T cell receptor down-modulation on CD8+ T cells". EMBO Molecular Medicine. 3 ... Chen DS, Mellman I (July 2013). "Oncology meets immunology: the cancer-immunity cycle". Immunity. 39 (1): 1-10. doi:10.1016/j. ... programmed cell death) of antigen-specific T-cells in lymph nodes. Second, it reduces apoptosis in regulatory T cells (anti- ... and on T cells and B cells upon TCR and B cell receptor signaling, whereas in resting mice, PD-L1 mRNA can be detected in the ...
"PD-L1 co-stimulation contributes to ligand-induced T cell receptor down-modulation on CD8+ T cells". EMBO Molecular Medicine. 3 ... Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ (July 2007). "Programmed death-1 ligand 1 interacts specifically with the ... Immunity. 27 (1): 111-22. doi:10.1016/j.immuni.2007.05.016. PMC 2707944. PMID 17629517. Karwacz K, Bricogne C, MacDonald D, ... It appears that (cancer-mediated) upregulation of PD-L1 on the cell surface may inhibit T cells that might otherwise attack. ...
Non-catalytic tyrosine-phosphorylated receptor
Yokosuka T, Takamatsu M, Kobayashi-Imanishi W, Hashimoto-Tane A, Azuma M, Saito T (June 2012). "Programmed cell death 1 forms ... A signaling cascade is initiated when the receptors bind their respective ligand resulting in cell activation. For that ... June 2010). "Constitutively active Lck kinase in T cells drives antigen receptor signal transduction". Immunity. 32 (6): 766-77 ... "What controls T cell receptor phosphorylation?". Cell. 142 (5): 668-9. doi:10.1016/j.cell.2010.08.018. PMID 20813251. Davis SJ ...
"Active systemic lupus erythematosus is associated with failure of antigen-presenting cells to express programmed death ligand-1 ... "PD-L1 co-stimulation contributes to ligand-induced T cell receptor down-modulation on CD8+ T cells". EMBO Molecular Medicine. 3 ... At that time it was concluded that B7-H1 helps tumor cells evade anti-tumor immunity. In 2003 B7-H1 was shown to be expressed ... PD-L1 is expressed on T cells, NK cells, macrophages, myeloid DCs, B cells, epithelial cells, and vascular endothelial cells. ...
... the infected cell may shut off its protein synthesis and may undergo programmed cell death (apoptosis). Immune cells that have ... natural killer cells, cells of the adaptive immunity T cells, and B cells, and non-immune cells (epithelial and endothelial ... Toll-like receptors and ligands database at University of Munich The Toll-Like Receptor Family of Innate Immune Receptors (pdf ... Kawai T, Akira S (May 2010). "The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors". ...
PD-L2 is one of two known ligands for Programmed cell death protein 1 (PD-1). PD-L2 is a cell surface receptor belonging to the ... May 2006). "No evidence for dualism in function and receptors: PD-L2/B7-DC is an inhibitory regulator of human T cell ... Chen L (May 2004). "Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity". Nature Reviews. ... April 2007). "Ligands for programmed cell death 1 gene in patients with systemic lupus erythematosus". The Journal of ...
... treated patients exhibit fold increases of peripheral CD8+ T cells expressing markers of activation, such as programmed death 1 ... The receptor complex for IL-10 also requires the IL10R2 chain to initiate signalling. This ligand-receptor combination is found ... "The β2-adrenergic receptor controls inflammation by driving rapid IL-10 secretion". Brain, Behavior, and Immunity. 74: 176-185 ... mast cells, CD4+CD25+Foxp3+ regulatory T cells, and in a certain subset of activated T cells and B cells. IL-10 can be produced ...
Cytotoxic T cell
... programmed cell death). Due to high lipid order and negatively charged phosphatidylserine present in their plasma membrane, TC ... or cells that are damaged in other ways. Most cytotoxic T cells express T-cell receptors (TCRs) that can recognize a specific ... molecules expressed on the target cell. However, this Fas-Fas ligand interaction is thought to be more important to the ... Venturi S, Venturi M (September 2009). "Iodine, thymus, and immunity". Nutrition. 25 (9): 977-9. doi:10.1016/j.nut.2009.06.002 ...
"The function of donor versus recipient programmed death-ligand 1 in corneal allograft survival". Journal of Immunology. 179 (6 ... "Corneal immunity is mediated by heterogeneous population of antigen-presenting cells". Journal of Leukocyte Biology. 74 (2): ... "Nonvascular VEGF receptor 3 expression by corneal epithelium maintains avascularity and vision". Proceedings of the National ... He is the director of the NIH-funded Harvard-Vision Clinical Scientist Development Program since 2004. "Research Profile: Reza ...
Extrinsic apoptopic pathway: The caspase cascade is also activated by extracellular ligands, via cell surface Death Receptors. ... Kumar, S (2006). "Caspase function in programmed cell death". Cell Death and Differentiation. 14 (1): 32-43. doi:10.1038/sj.cdd ... "Caspases Connect Cell-Death Signaling to Organismal Homeostasis". Immunity. 44 (2): 221-231. doi:10.1016/j.immuni.2016.01.020. ... Caspases have other identified roles in programmed cell death such as pyroptosis and necroptosis. These forms of cell death are ...
Major histocompatibility complex
... the CTL triggers the cell to undergo programmed cell death by apoptosis. Thus, MHC class I helps mediate cellular immunity, a ... A CTL expresses CD8 receptors, in addition to T-cell receptors (TCR)s. When a CTL's CD8 receptor docks to a MHC class I ... the antigen/ligand for many of these molecules remain unknown, but they can interact with each of CD8+ T cells, NKT cells, and ... B cells express MHC class II to present antigens to Th0, but when their B cell receptors bind matching epitopes, interactions ...
The siRNA inhibition of IRAK4 in mice displayed greater programmed cell death (PCD) and slowed tumor growth. This experimental ... or Toll-like receptor-mediated immune responses (TLR), but was not essential to T-cell Receptor (TCR) signalling as was ... The ligand binding causes conformational changes to the intracellular domain which allows for the recruitment of scaffolding ... Children with IRAK4 deficiency have been found to have decreased immunity to some specific bacterial infections yet not to ...
Ced-family members contain a caspase recruitment domain (CARD) and are known to be key mediators of programmed cell death. The ... Mouse NLRP1B is not activated by a receptor-ligand type mechanism. NLRP1B variants from certain inbred mouse strains, BALB/c ... December 2012). "NLRP1 inflammasome activation induces pyroptosis of hematopoietic progenitor cells". Immunity. 37 (6): 1009-23 ... May 2015). "A Plant Immune Receptor Detects Pathogen Effectors that Target WRKY Transcription Factors". Cell. 161 (5): 1089- ...
Programmed cell death-1 (PD-1) is heavily expressed on T cells at the tumor site than on T cells present in the peripheral ... "The ligands of CXC chemokine receptor 3, I-TAC, Mig, and IP10, are natural antagonists for CCR3". The Journal of Biological ... Th1 cells produce IFN-γ, TNF-α, IL-2 and enhance anti-tumor immunity by stimulating CTLs, NK cells and macrophages. The IFN-γ- ... Immune cells, like Th1, CTLs, NK cells, and NKT cells, show anti-tumor effect against cancer cells through paracrine CXCL9/ ...
The approval of anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed cell death protein 1 (PD-1) ... March 2005). "CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally ... The virus integrates the receptor into the T cells' genome. The cells are expanded non-specifically and/or stimulated. The ... activating them with different TLR ligands, cytokine combinations, and injecting them back to the patients. The in vivo ...
Th 9 cell
Activin A that can fully substitute the role of TGF-β in TH9 cells, then Jagged2, programmed cell death ligand (PD-L2), ... "Notch Receptors and Smad3 Signaling Cooperate in the Induction of Interleukin-9-Producing T Cells". Immunity. 36 (4): 623-634. ... In cell biology, TH9 cells (T helper type 9 cells, CD4+IL-9+IL-13−IFNγ − ) are a sub-population of CD4+T cells that produce ... "Programmed cell death ligand 2 regulates TH9 differentiation and induction of chronic airway hyperreactivity". The Journal of ...
Selective serotonin reuptake inhibitor
SSRIs can also induce apoptosis, programmed cell death, in T-cells. The full mechanism of action for the anti-inflammatory ... ligands of the sigma receptors. Fluvoxamine is an agonist of the σ1 receptor, while sertraline is an antagonist of the σ1 ... Evidence shows that SSRIs can inhibit proliferation in T-cells, which are important cells for adaptive immunity and can induce ... Vilazodone is a 5-HT1A receptor partial agonist while vortioxetine is a 5-HT1A receptor agonist and 5-HT3 and 5-HT7 receptor ...
T helper cell
T lymphocytes augments lymphokine-induced B cell Ig isotype switch recombination and rescues B cells from programmed cell death ... Like all T cells, they express the T cell receptor-CD3 complex. The T cell receptor (TCR) consists of both constant and ... The main effector cells of Th1 immunity are macrophages as well as CD8 T cells, IgG B cells, and IFN-γ CD4 T cells. The key Th1 ... CD154, also called CD40 ligand or CD40L, is a cell surface protein that mediates T cell helper function in a contact-dependent ...
There is evidence that VISTA can act as both a ligand and a receptor on T cells to inhibit T cell effector function and ... Another ongoing clinical trial involves a small molecule that antagonizes the programmed death-ligands 1 and 2 (PD-L1 and PD-L2 ... T cell-mediated immunity". Journal of Clinical Investigation. 124 (5): 1966-75. doi:10.1172/JCI74589. PMC 4001557. PMID ... "Characterization of programmed death-1 homologue-1 (PD-1H) expression and function in normal and HIV infected individuals". ...
... and TNF receptor-induced cell death". Cell. 85 (6): 803-15. doi:10.1016/s0092-8674(00)81265-9. PMID 8681376. S2CID 7415784. ... This protein is involved in the programmed cell death induced by Fas and various apoptotic stimuli. The N-terminal FADD-like ... Gajate C, Mollinedo F (March 2005). "Cytoskeleton-mediated death receptor and ligand concentration in lipid rafts forms ... Shu HB, Halpin DR, Goeddel DV (June 1997). "Casper is a FADD- and caspase-related inducer of apoptosis". Immunity. 6 (6): 751- ...
Primary effusion lymphoma
... which inhibits host cells' p53 protein thereby reducing these cells' apoptosis (i.e. programmed cell death) response to injury ... K1 protein which promotes the malignancy of host cells; 7) G-protein coupled receptor protein which promotes host cells' ... the decline in immunity that develops with aging, and/or cirrhosis of the liver due to hepatitis B or C virus. The plasmacytoid ... overexpression of the P-selectin glycoprotein ligand-1 gene whose protein product promotes cell attachment to vascular ...
... a form of programmed cell death). PANoptosis is defined as a unique, physiologically relevant, inflammatory programmed cell ... Her research interests include innate immunity and inflammatory cell death with a primary focus on the role of NLR proteins and ... "IRGB10 Liberates Bacterial Ligands for Sensing by the AIM2 and Caspase-11-NLRP3 Inflammasomes". Cell. 167 (2): 382-396.e17. doi ... Kanneganti is well known for her breakthrough discoveries elucidating functions of innate immune receptors, inflammasomes, and ...
Cell-mediated immunity: Delayed hypersensitivity and cytotoxic responses are mediated by different T-cell subclasses. J Exp Med ... Weber GF, Ashkar S, Glimcher MJ, Cantor H. Receptor-ligand interaction between Osteopontin (Eta-1) and CD44. Science 271: 509- ... Inactivation of mis-selected CD8 T cells by CD8 gene methylation and cell death. Science 284: 1187-1191. Ashkar S, Weber GF, ... Harvard Medical School Program in Immunology profile . ... receptor on dendritic cells inhibits promotion of Th17 cells: ...
Mesenchymal stem cell
Davies LC, Heldring N, Kadri N, Le Blanc K (March 2017). "Mesenchymal Stromal Cell Secretion of Programmed Death-1 Ligands ... May 2012). "Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis". Cell Stem Cell ... MSCs have an effect on macrophages, neutrophils, NK cells, mast cells and dendritic cells in innate immunity. MSCs are able to ... MSCs also reduce the expression of NK cell receptors - NKG2D, NKp44 and NKp30. MSCs inhibit respiratory flare and apoptosis of ...
... is an immune checkpoint and together with other inhibitory receptors including programmed cell death protein 1 (PD-1) ... "T cell immunoglobulin mucin-3 crystal structure reveals a galectin-9-independent ligand-binding surface". Immunity. 26 (3): 311 ... Later, the expression was detected in Th17 cells, regulatory T-cells, and innate immune cells (dendritic cells, NK cells, ... The engagement leads to stimulation of an influx of calcium to intracellular space and induction of programmed cell death, ...
T helper cell
T lymphocytes augments lymphokine-induced B cell Ig isotype switch recombination and rescues B cells from programmed cell death ... Like all T cells, they express the T cell receptor-CD3 complex. The T cell receptor (TCR) consists of both constant and ... Antitumor immunity. Main article: CD4+ T cells and antitumor immunity. Hypersensitivity. The immune system must ... CD154, also called CD40 ligand or CD40L, is a cell surface protein that mediates T cell helper function in a contact-dependent ...
"Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection". Nature ... "Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility ... As a part of the vertebrate innate immune system monocytes also influence the process of adaptive immunity. There are at least ... Vacuolization may be present in a cell that has recently phagocytized foreign matter. Many factors produced by other cells can ...
Death receptor 3
"TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator". Immunity. 16 (3): 479-92. doi:10.1016/ ... The alternative splicing of this gene in B and T cells encounters a programmed change upon T-cell activation, which ... Death receptor 3 (DR3), also known as tumor necrosis factor receptor superfamily member 25 (TNFRSF25), is a cell surface ... which is rapidly upregulated in antigen presenting cells and some endothelial cells following Toll-Like Receptor or Fc receptor ...
... and TNF receptor-induced cell death". Cell. 85 (6): 803-15. doi:10.1016/S0092-8674(00)81265-9. PMID 8681376. S2CID 7415784. ... this gene is a death domain containing adaptor molecule that interacts with TNFRSF1A/TNFR1 and mediates programmed cell death ... Pan G, O'Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, Dixit VM (April 1997). "The receptor for the cytotoxic ligand TRAIL ... Immunity. 7 (6): 821-30. doi:10.1016/S1074-7613(00)80400-8. PMID 9430227. Pan G, Bauer JH, Haridas V, Wang S, Liu D, Yu G, ...
TIM-3 acts as a negative regulator of Th1/Tc1 function by triggering cell death upon interaction with its ligand, galectin-9. ... KIR: short for Killer-cell Immunoglobulin-like Receptor, is a receptor for MHC Class I molecules on Natural Killer cells. ... short for Programmed Death 1 (PD-1) receptor, has two ligands, PD-L1 and PD-L2. This checkpoint is the target of Merck & Co.'s ... "CD27 is required for generation and long-term maintenance of T cell immunity". Nat Immunol. 1 (5): 433-40. doi:10.1038/80877. ...
Programmed Death Ligand-1 (PD-L1) Expression in the Programmed Death Receptor-1 (PD-1)/PD-L1 Blockade: A Key Player Against...
Expression in the Programmed Death Receptor-1 (PD-1)/PD-L1 Blockade: A Key Player Against Various Cancers.(Report) by Archives ... attenuates the amplitude of T-cell receptor (TCR)-mediated immunity. Abbreviation: MHC, major histocompatibility complex. Table ... Ligand-1+(PD-L1)+Expression+in+the+Programmed+Death...-a0508360875. *APA style: Programmed Death Ligand-1 (PD-L1) Expression in ... Programmed+Death...-a0508360875,/a,. Citations: *MLA style: "Programmed Death Ligand-1 (PD-L1) Expression in the Programmed ...
JCI - Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade-mediated tumor regression
Kupffer cell suppression of CD8+ T cells in human hepatocellular carcinoma is mediated by B7-H1/programmed death-1 interactions ... Programmed death-ligand 1 (PD-L1) expression on tumor cells is essential for T cell impairment, and PD-L1 blockade therapy has ... Host immunity determines anti-PD-L1-induced tumor immunity. To determine whether host immunity plays a role in the efficacy of ... Therapeutic blockade of programmed death-ligand 1 (PD-L1, B7-H1) or programmed death protein 1 (PD-1) with mAbs leads to ...
Activation of p53/miR-34a Tumor Suppressor Axis by Chinese Herbal Formula JP-1 in A549 Lung Adenocarcinoma Cells
MiR-34a is an important p53 downstream tumor suppressor, which regulates apoptosis, cell-cycle, EMT (epithelial mesenchymal ... implying its inhibitory effect on the energy-sensitive protein synthesis and cell proliferation signaling. Our results show ... Here, we show that a Chinese herbal formula JP-1 activates p53/miR-34a axis in A549 human LADC cells (p53 wild-type). Treatment ... Lung cancer is the leading cause of cancer death worldwide; the most common pathologic type is lung adenocarcinoma (LADC). In ...
Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors | Clinical...
The programmed death receptor 1 (PD-1) pathway is an immune checkpoint inhibitor exploited by tumor cells to suppress antitumor ... dampens T-cell receptor signaling, leading to downregulation of T-cell activation, proliferation, and T-cell-mediated antitumor ... programmed death ligands 1 and 2 (PD-L1 and PD-L2), ... immunity. Pembrolizumab (MK-3475) is a potent, highly selective ... Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose- ...
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. - PubMed - NCBI
Programmed death-ligand 1 (PD-L1; also called B7-H1 or CD274), which is expressed on many cancer and immune cells, plays an ... Binding of PD-L1 to its receptors suppresses T-cell migration, proliferation and secretion of cytotoxic mediators, and ... important part in blocking the cancer immunity cycle by binding programmed death-1 (PD-1) and B7.1 (CD80), both of which are ... Markers of tumour-infiltrating immune cells: CD163 (macrophages), CD11c (dendritic cells) and CD3 (T cells). Marker of tumour ...
Suppressed Programmed Death 1 Expression on CD4+ and CD8+ T Cells in Psoriatic Patients
... biological response modifiers and the family of cell adhesion-promoting molecules. ... D. S. Kim, J. H. Je, S. H. Kim et al., "Programmed death-ligand 1, 2 expressions are decreased in the psoriatic epidermis," ... X. Zhang, J. C. Schwartz, X. Guo et al., "Structural and functional analysis of the costimulatory receptor programmed death-1 ... Immunity, vol. 20, no. 3, pp. 337-347, 2004. View at Publisher · View at Google Scholar · View at Scopus ...
Programmed death ligand-1 over-expression correlates with malignancy and contributes to immune regulation in ovarian cancer |...
... pathway is important in the maintenance of peripheral tolerance and homeostasis through suppression of T cell receptor ... Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 9(5):562-567. doi: 10.1038/nm863 PubMed ... We show programmed death ligand-1 (PD-L1) expression on monocytes in the ascites and blood of patients with malignant OC is ... Programmed death ligand-1 over-expression correlates with malignancy and contributes to immune regulation in ovarian cancer. ...
Clinical Trial Summary: Adult Lymphoma Program - Dana-Farber Cancer Institute | Boston, MA
Adult Lymphoma Program operates a large and growing research program. While we are testing many exciting and active drugs, we ... and B-cell co-receptor whose ligands are expressed on macrophage-lineage and endothelial cells, as well as by many tumor cells ... which target the inhibitory T-cell co-receptor CTLA-4, thereby relieving T-cell inhibition and enhancing antitumor immunity, ... Another immunomodulatory target is programmed cell death-1 (PD-1), an inhibitory T- ...
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients
These changes distinguish cancer cells from their normal counterparts, allowing tumours to be recognized as foreign by the ... Programmed death-ligand 1 (PD-L1; also called B7-H1 or CD274), which is expressed on many cancer and immune cells, plays an ... Binding of PD-L1 to its receptors suppresses T-cell migration, proliferation and secretion of cytotoxic mediators, and ... important part in blocking the cancer immunity cycle by binding programmed death-1 (PD-1) and B7.1 (CD80), both of which are ...
Therapeutic PD-1 Pathway Blockade Augments with Other Modalities of Immunotherapy T-Cell Function to Prevent Immune Decline in...
Tumor-infiltrating programmed death receptor-1+ dendritic cells mediate immune suppression in ovarian cancer.J Immunol 2011;186 ... programmed cell death ligand 1 (PD-L1) and PD-L2 called B7-H1 and B7-DC, respectively (8, 9). Tumors can use the PD-1 ... Regulation of T cell immunity by dendritic cells. Cell 2001;106:263-6. ... is an inhibitory surface receptor expressed by T cells, B cells, natural killer T cells, monocytes, and dendritic cells (DC), ...
The blockade of immune checkpoints in cancer immunotherapy. - PubMed - NCBI
... killer cell immunoglobulin-like receptor; LAG3, lymphocyte activation gene 3; PD1, programmed cell death protein 1; PDL, PD1 ... Depicted are various ligand-receptor interactions between T cells and antigen-presenting cells (APCs) that regulate the T cell ... Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune ... activated T cells upregulate ligands, such as CD40L, that engage cognate receptors on APCs. A2aR, adenosine A2a receptor; B7RP1 ...
A Cysteine-Rich Protein Kinase Associates with a Membrane Immune Complex and the Cysteine Residues Are Required for Cell Death ...
2003) Sensitization of defense responses and activation of programmed cell death by a pathogen-induced receptor-like protein ... PDLPs are involved in the regulation of plant cell-to-cell communication, viral cell-to-cell movement, and plant immunity ( ... PTI receptors are receptor-like kinases (RLKs) or receptor-like proteins (RLPs) possessing extracellular ligand-binding domains ... Cell death was observed for wild-type CRK28, whereas no cell death was observed for Cys mutants. The leaf was photographed 48 ...
IL-15 Regulates CD8+ T Cell Contraction during Primary Infection | The Journal of Immunology
... and TNF in antigen-induced programmed cell death in T cell receptor transgenic mice. Immunity 5: 17-30. ... Fas(CD95)/Fas-ligand interactions required for programmed cell death after T cell activation. Nature 373: 444-448. ... At least two types of cell death can occur in activated T cells during the contraction phase: activation-induced cell death (3 ... 3 Abbreviations used in this paper: ACAD, activated T cell autonomous cell death; cγ, common cytokine receptor γ; LCMV, ...
T-cell co-stimulatory molecules: their role in allergic immune reactions | European Respiratory Society
CD40 ligand; Tm: memory T-cell; OX40: CD134; OX40L: OX40 ligand; Tr: regulatory T-cell; PD: programmed cell death. ... Ox40-ligand has a critical costimulatory role in dendritic cell:T cell interactions. Immunity 1999;11:689-698. ... APC: antigen-presenting cell; MHC: major histocompatibility complex; TCR: T-cell receptor; IL: interleukin; Eos: eosinophil; Ig ... Signalling through the negative co-stimulatory molecule, programmed cell death (PD)-1, leads to arrest in cell cycle phase G0-G ...
Frontiers | Glyco-Engineered Anti-Human Programmed Death-Ligand 1 Antibody Mediates Stronger CD8 T Cell Activation Than Its...
No differences were observed regarding binding to PD-L1 and blocking of this interaction with its counter receptors PD-1 or ... axis plays a central role in suppression of anti-tumor immunity. Blocking the axis by targeting PD-L1 with monoclonal ... No differences were observed regarding binding to PD-L1 and blocking of this interaction with its counter receptors PD-1 or ... activity against PD-L1+ cancer cells compared to the ... The PD-1/PD-L1 axis plays a central role in suppression of anti ...
Frontiers | Functional Expression of Programmed Death-Ligand 1 (B7-H1) by Immune Cells and Tumor Cells | Immunology
This suggests that PD-L1 expressed by non-malignant cells may also contribute to anti-tumor immunity. Here we review the ... This suggests that PD-L1 expressed by non-malignant cells may also contribute to anti-tumor immunity. Here we review the ... The influence of PD-L1 expressed by tumor cells on anti-tumor CD8+ T cell responses is well characterized, but the impact of PD ... The influence of PD-L1 expressed by tumor cells on anti-tumor CD8+ T cell responses is well characterized, but the impact of PD ...
Programmed cell death ligand 1 cut-point is associated with reduced disease specific survival in resected pancreatic ductal...
A predictive biomarker to this class of drugs has not been clearly identified; however, overexpression of the PD1 ligand (PD-L1 ... for tumor cell membrane staining. Two-hundred fifty-two cases were included in the TMA and evaluable by IHC. Thirty-one (12%), ... Programmed cell death 1 (PD1) inhibitors have recently shown promising anti-cancer effects in a number of solid tumor types. ... Survival analysis was performed using three thresholds (> = 1%, >5% and >10%) ...
The blockade of immune checkpoints in cancer immunotherapy
Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune ... Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 ( ... Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies ... Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune ...
Programmed Death Ligand 1 Is Expressed by Non-Hodgkin Lymphomas and Inhibits the Activity of Tumor-Associated T Cells |...
Its ligand, PD-L1 (B7-H1/CD274), is expressed on antigen-presenting cells. Binding of PD-L1 to its receptor inhibits T-cell ... B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders. Blood 2009;114:2149-58. ... Schistosoma mansoni worms induce anergy of T cells via selective up-regulation of programmed death ligand 1 on macrophages. J ... Expression of the negative T-cell regulator programmed death ligand 1 (PD-L1) seems to facilitate immune tolerance of various ...
Durable antitumor responses to CD47 blockade require adaptive immune stimulation | PNAS
Durable tumor immunity required programmed death-ligand 1 (PD-L1) blockade in combination with an antitumor antibody, with ... IFN-γ induces a myriad of changes to the cell surface receptor repertoire on both tumor cells and immune cells (40, 41). In the ... Expression of programmed death-ligand 1 (PD-L1) on tumors delivers an inhibitory signal to T cells upon ligation with its ... However, when combined with blockade of programmed death-ligand 1 (PD-L1), an immune receptor that inhibits antitumor T cell ...
Cancers | Free Full-Text | Low CD8+ T Cell Infiltration and High PD-L1 Expression Are Associated with Level of CD44+/CD133+...
However, the clinical implications of the associations among CD8+ T cells infiltration, programmed death receptor ligand-1 (PD- ... Both the low CD8+ T cells infiltration/high PD-L1 expression group and the high CD8+ T cells infiltration/high PD-L1 expression ... CD8+ T cells infiltration was associated with better survival while PD-L1 expression was correlated with PC recurrence. ... Moreover, high infiltration of CD8+ T cells could reduce unfavorable prognostic effect of high co-expression of PD-L1 and CD44/ ...
JCI - Rationale for hypoxia assessment and amelioration for precision therapy and immunotherapy studies
Further, only one immunotherapy trial is examining whether hypoxia reduces immunotherapy efficacy to programmed cell death 1 ( ... increasing programmed death ligand 1 (PD-L1) expression via the HIF-1 pathway, and promoting secretion of immunosuppressive ... and affects NK cell function by reducing expression of the activating receptor NKG2D (7). With respect to the adaptive immune ... Hypoxia influences efficacy of immunotherapy via several mechanisms, including both innate and adaptive immunity. For example, ...
PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16...
The receptor programmed death-1 (PD-1) is also expressed on T cells following activation, where, on binding to its ligands PD- ... Recently, an additional coinhibitory ligand/receptor interaction has been described that involves binding of PD-L1 on T cells ... Induction of T-cell Immunity Overcomes Complete Resistance to PD-1 and CTLA-4 Blockade and Improves Survival in Pancreatic ... the T-cell fraction was enriched using a Miltenyi T-cell purification kit. A total of 2 × 105 CD8 cells and 2.5 × 105 CD4 cells ...
NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 4.2016 in: Journal of the National Comprehensive Cancer Network...
that target the programmed cell death protein 1 (PD-1) cell surface receptor. By blocking the interaction of PD-1 and ... programmed death-ligand 1 (PD-L1), treatment is hypothesized to improve antitumor immunity. The PD-1 pathway is one prominent ... allowing cytotoxic T cells to be activated. These activated T cells can then recognize and kill tumor cells.12,14 Other immune ... Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med2015;373:123-135. ...
JCI Insight - Monocyte dysregulation and systemic inflammation during pediatric falciparum malaria
iMFI, integrated mean fluorescence intensity; BAFF, B cell-activating factor; PD-L1, programmed death-ligand 1. ... Cell surface expression of markers important in innate immunity: TLR2, TLR4, and CD36. (B) Cell surface expression of markers ... BAFF and BAFF receptor levels correlate with B cell subset activation and redistribution in controlled human malaria infection ... Programmed death-ligand 1 (PD-L1), which delivers inhibitory signals upon binding to its receptor on T cells, had increased ...
The tumor microenvironment consists of both tumor cells | Open-i
The tumor microenvironment consists of both tumor cells and other cell types such as immature myeloid-derived suppressor cells ... Programmed death-ligand 1 and its receptor) . Naturally occurring anti-tumor T lymphocytes previously controlled by immune ... Gene engineered chimeric antigen receptor (CAR) T lymphocytes have also shown spectacular results in B cell malignancy after ... The aim of immunostimulatory gene therapy is to tilt the suppressive tumor microenvironment to promote anti-tumor immunity. ...
A critical role for the programmed death ligand 1 in fetomaternal tolerance | Journal of Experimental Medicine | Rockefeller...
The role of the ICOS-B7h T cell costimulatory pathway in transplantation immunity. J. Clin. Invest. ... PDL1 has been shown also to interact with a putative receptor other than PD1 to deliver positive stimulatory signals for T cell ... Here we show that the inhibitory T cell costimulatory molecule, programmed death ligand 1 (PDL1), has an important role in ... A critical role for the programmed death ligand 1 in fetomaternal tolerance Indira Guleria Indira Guleria ...
Classifying Cancers Based on T-cell Infiltration and PD-L1 | Cancer Research
T cells) from interacting with their ligands CD80/CD86 or PD-L1/PD-L2 (program death ligand 1/2), respectively (9, 10). This ... Immune checkpoint receptors on immune cells, when engaged by their ligands, transmit an inhibitory signal, maintain self- ... Anti-TIM3 antibody promotes T cell IFN-γ-mediated antitumor immunity and suppresses established tumors. Cancer Res 2011;71:3540 ... Programmed death ligand 2 in cancer-induced immune suppression. Clin Dev Immunol 2012;2012:656340. ...
Hong Namkoong | Stanford Medicine Profiles
... from patients with CAD spontaneously expressed high surface density of the immunoinhibitory ligand programmed death ligand-1 ( ... Pyruvate controls the checkpoint inhibitor PD-L1 and suppresses T cell immunity. The Journal of clinical investigation Watanabe ... Diversification of the antigen-specific T cell receptor repertoire after varicella zoster vaccination. Science translational ... PD-L1), thereby providing negative signals to programmed death-1+ (PD-1+) T cells. We determined that aberrant PD-L1 expression ...
PD-L1 regulates the development, maintenance, and function of induced regulatory T cells | JEM
programmed death. PD-L. PD-ligand. T eff. effector T. T reg. regulatory T. ... Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity. 29:44-56. doi:10.1016/j.immuni. ... glucocorticoid-induced TNF receptor), require prior stimulation for T reg cell activity, and potently suppress T eff cells ( ... C) PD-L1 iT reg cells suppress T eff cells more effectively than control iT reg cells. CD4+CD62L+ FoxP3.GFP− naive T cells were ...
AntitumorSignaling moleculesBlockadeEffector T celHumanized monoclonProliferationMicroenvironmentDendriticImmunotherapyCD28TumorsBindsInducesAntigen receptorResponsesProteinInnate and adaptive immunityApoptosisAdaptiveAntibodiesCD274InteractionImmunosuppressiveInhibitsPathwayCD80MelanomaExtracellularMoleculeMacrophagesInfectionInhibitionLymphocytesCytokineActivationAntigensInduceMiceHost immunityTumor-specificPeripheralImmunologyAPCsAnti-tumorVitroExhaustionRegulatesImmune cellsSquamous Cell CarcNivolumabCheckpoint inhibitorPembrolizumabInhibitory receptorsInhibitMonoclonalRegulatory T celMonocytesTherapeutic
- During the past several decades, the efforts of antitumor immune therapy have been focused on identification of specific tumor antigens to augment antitumor immunity. (thefreelibrary.com)
- The programmed death receptor 1 (PD-1) pathway is an immune checkpoint inhibitor exploited by tumor cells to suppress antitumor immunity. (aacrjournals.org)
- Drugs like Ipilimumab, which target the inhibitory T-cell co-receptor CTLA-4, thereby relieving T-cell inhibition and enhancing antitumor immunity, have had success in treating melanoma. (dana-farber.org)
- The tumor microenvironment mediates induction of the immunosuppressive programmed cell death-1 (PD-1) pathway, and targeted interventions against this pathway can help restore antitumor immunity. (aacrjournals.org)
- This indicates that, although antitumor immunity is elicited against ovarian cancer, it is counterbalanced by immunosuppressive factors. (aacrjournals.org)
- These therapies, referred to here as PD-L1/PD-1 checkpoint blockade therapies, are designed to block the interaction between PD-L1, expressed by tumor cells, and PD-1, expressed by tumor-infiltrating CD8 + T cells, leading to enhanced antitumor CD8 + T cell responses and tumor regression. (frontiersin.org)
- The influence of PD-L1 expressed by tumor cells on antitumor CD8 + T cell responses is well characterized, but the impact of PD-L1 expressed by immune cells has not been well defined for antitumor CD8 + T cell responses. (frontiersin.org)
- This suggests that PD-L1 expressed by non-malignant cells may also contribute to antitumor immunity. (frontiersin.org)
- Here, we review the functions of PD-L1 expressed by immune cells in the context of CD8 + T cell priming, contraction, and differentiation into memory populations, as well as the role of PD-L1 expressed by tumor cells in regulating antitumor CD8 + T cell responses. (frontiersin.org)
- Interruption of CD47-SIRPα interactions in immunodeficient mice bearing human tumors enhances therapeutic antitumor antibody responses by promoting phagocytosis of antibody-bound tumor cells. (pnas.org)
- However, when combined with blockade of programmed death-ligand 1 (PD-L1), an immune receptor that inhibits antitumor T cell responses, we find synergistic activity, suggesting a role for both innate and adaptive inhibitory pathways in the response to therapeutic antibodies. (pnas.org)
- Therapeutic antitumor antibodies treat cancer by mobilizing both innate and adaptive immunity. (pnas.org)
- Here, we show that CD47 blockade alone or in combination with a tumor-specific antibody fails to generate antitumor immunity against syngeneic B16F10 tumors in mice. (pnas.org)
- Durable tumor immunity required programmed death-ligand 1 (PD-L1) blockade in combination with an antitumor antibody, with incorporation of CD47 antagonism substantially improving response rates. (pnas.org)
- PD-L1 is aberrantly expressed on some epithelial malignancies and Hodgkin lymphomas and may prevent effective host antitumor immunity. (aacrjournals.org)
- Antibody blockade of CTLA-4 or PD-1 has been shown to enhance antitumor immune responses in both murine preclinical models and clinical trials ( 2 , 5 ). (pnas.org)
- Anti-CTLA-4 and anti-PD-1 are thought to mediate their antitumor activity by blocking CTLA-4 or PD-1 on effector immune cells (such as CD8 + T cells) from interacting with their ligands CD80/CD86 or PD-L1/PD-L2 (program death ligand 1/2), respectively ( 9, 10 ). (aacrjournals.org)
- This release of suppression on effector cells thus allows their full antitumor function to be exerted. (aacrjournals.org)
- These inhibitory pathways, known as "checkpoints," are also exploited by tumors to dampen and evade antitumor immunity. (prolekare.cz)
- Thus, Id2kd tumor cells can be used as whole cell vaccines, in which the altered tumor cells themselves are administered back to the host as a vaccine to induce antitumor immunity. (prolekare.cz)
- Purpose Hodgkin Reed-Sternberg (HRS) cells evade antitumor immunity by multiple means, including gains of 9p24.1/ CD274(PD-L1)/ PDCD1LG2(PD-L2) and perturbed antigen presentation. (elsevier.com)
- Combining cancer vaccines with CPIs or other anti-cancer drugs, like gemcitabine and sunitinib, known to counteract myeloid-derived suppressor cell (MDSC)-derived immunosuppression [ 7 ] may thus provide the necessary stimulation to broaden the repertoire of T cells engaged in the antitumor response. (springer.com)
- Weak and ineffective antitumor cytotoxic T lymphocyte (CTL) responses can be rescued by immunomodulatory mAbs targeting PD-1 or CD137. (aacrjournals.org)
- We show that cross-priming of tumor antigens by BATF3-dependent DCs is a key limiting factor that can be exploited to enhance the antitumor efficacy of anti-PD-1 and anti-CD137 immunostimulatory mAbs. (aacrjournals.org)
- Therefore, improving the capacity of modified-T cells to specifically degrade the ECM in stroma-rich solid tumors, yet without compromising their cytotoxicity, would enhance their antitumor activity. (biomedcentral.com)
- The cells were more responsive to interferon-γ, leading to increased secretion of cytokines that promote antitumor immunity. (sciencemag.org)
- We used a genome-scale CRISPR-Cas9 screen to identify mechanisms of tumor cell resistance to killing by cytotoxic T cells, the central effectors of antitumor immunity. (sciencemag.org)
- Finally, VISTA overexpression on tumor cells interferes with protective antitumor immunity in vivo in mice. (rupress.org)
- The programmed death-1 receptor (PD‑1) on T cells normally helps limit excessive immune activation, but it can also suppress beneficial antitumor immunity. (jci.org)
- Immune checkpoint inhibitors are becoming a cornerstone of cancer immunotherapy as a result of their clinical success in relieving immune suppression and driving durable antitumor T cell responses in certain subsets of patients. (jci.org)
- Therefore, abrogating the PD-1/PD-L1 interaction with therapeutic antibodies has been explored as a means to enhance antitumor immunity. (elsevier.com)
- Here we show that resistance to an effective antitumor immune response is also a result of IFN signaling in a different cellular compartment of the tumor, the cancer cells themselves. (jci.org)
- This result helps explain why radiation of tumors can stimulate antitumor immunity yet also result in resistance. (jci.org)
- These antagonist monoclonal antibodies are capable of unleashing dormant or exhausted antitumor immunity, which has led to durable complete and partial responses in a large number of patients. (biomedcentral.com)
- In order to achieve antitumor effects, cytotoxic T lymphocytes (CTL) must not only migrate to the tumor, but must also be capable of tumor cell lysis. (biomedcentral.com)
- This therapeutic effect was associated with increased proliferation and function of tumor antigen-specific effector CD8 + T cells, inhibition of suppressive regulatory T cells (Treg) and MDSC, upregulation of effector T-cell signaling molecules, and generation of T memory precursor cells. (aacrjournals.org)
- PD-L1 iT reg cell development is mediated through the down-regulation of phospho-Akt, mTOR, S6, and ERK2 and concomitant with the up-regulation of PTEN, all key signaling molecules which are critical for iT reg cell development. (rupress.org)
- Programmed Death Ligand-1 (PD-L1) Expression in the Programmed Death Receptor-1 (PD-1)/PD-L1 Blockade: A Key Player Against Various Cancers. (thefreelibrary.com)
- PD-1 blockade augments Th1 and Th17 and suppresses Th2 responses in peripheral blood from patients with prostate and advanced melanoma cancer," Journal of Immunotherapy , vol. 35, no. 2, pp. 169-178, 2012. (hindawi.com)
- When combined with GVAX or FVAX vaccination (consisting of irradiated ID8 cells expressing granulocyte macrophage colony-stimulating factor or FLT3 ligand) and costimulation by agonistic α-4-1BB or TLR 9 ligand, antibody-mediated blockade of PD-1 or PD-L1 triggered rejection of ID8 tumors in 75% of tumor-bearing mice. (aacrjournals.org)
- Overall, PD-1/PD-L1 blockade enhanced the amplitude of tumor immunity by reprogramming suppressive and stimulatory signals that yielded more powerful cancer control. (aacrjournals.org)
- Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. (nih.gov)
- Although PD-L1 expression by tumor cells has been used as a biomarker in selection of patients for PD-L1/PD-1 checkpoint blockade therapies, patients whose tumor cells lack PD-L1 expression often respond positively to PD-L1/PD-1 checkpoint blockade therapies. (frontiersin.org)
- The therapeutic potential of PD-1/PD-L1 blockade has been demonstrated in multiple cancer mouse models ( 13 , 14 ) and in human clinical trials ( 15 - 19 ). (frontiersin.org)
- In autologous cultures of primary ALCL and DLBCL, PD-L1 blockade enhanced secretion of inflammatory cytokines IFN-γ, granulocyte macrophage colony-stimulating factor, interleukin (IL)-1, IL-6, IL-8, IL-13, TNF-α, and macrophage inflammatory protein-1α. (aacrjournals.org)
- In vitro experiments using established cell lines and primary lymphoma specimens show that both T-cell and B-cell lymphomas express biologically active PD-L1 and that suppression of tumor-associated T cells can be reversed by PD-L1 blockade. (aacrjournals.org)
- Vaccination with irradiated B16 melanoma cells expressing either GM-CSF (Gvax) or Flt3-ligand (Fvax) combined with antibody blockade of the negative T-cell costimulatory receptor cytotoxic T-lymphocyte antigen-4 (CTLA-4) promotes rejection of preimplanted tumors. (pnas.org)
- Despite CTLA-4 blockade, T-cell proliferation and cytokine production can be inhibited by the interaction of programmed death-1 (PD-1) with its ligands PD-L1 and PD-L2 or by the interaction of PD-L1 with B7-1. (pnas.org)
- Here, we show that the combination of CTLA-4 and PD-1 blockade is more than twice as effective as either alone in promoting the rejection of B16 melanomas in conjunction with Fvax. (pnas.org)
- Combination PD-1 and CTLA-4 blockade increases effector T-cell (Teff) infiltration, resulting in highly advantageous Teff-to-regulatory T-cell ratios with the tumor. (pnas.org)
- Combination blockade also synergistically increases Teff-to-myeloid-derived suppressor cell ratios within B16 melanomas. (pnas.org)
- These results suggest that combination blockade of the PD-1/PD-L1- and CTLA-4-negative costimulatory pathways allows tumor-specific T cells that would otherwise be inactivated to continue to expand and carry out effector functions, thereby shifting the tumor microenvironment from suppressive to inflammatory. (pnas.org)
- Previously, we have shown that vaccination with B16-GM-CSF (Gvax) or B16-Flt3-ligand (Fvax) promotes the rejection of preimplanted B16-BL6 melanomas when combined with antibody blockade of CTLA-4 ( 6 , 7 ). (pnas.org)
- Further, only one immunotherapy trial is examining whether hypoxia reduces immunotherapy efficacy to programmed cell death 1 (PD-1) and CTLA-4 blockade with nivolumab and ipilimumab, respectively (NCT03003637). (jci.org)
- NCT03575598 will examine effects of immunotherapy with a tyrosine kinase inhibitor, sitravatinib, and PD-1 blockade with nivolumab in patients with head and neck cancer. (jci.org)
- Central to the efficacy of immune checkpoint blockade is the requirement for immune cells to infiltrate into tumors. (aacrjournals.org)
- A different approach is to block the inhibitory signaling that would otherwise restrain CTLs by using checkpoint blockade antibodies targeting CTLA-4 (CTL-associated protein 4) or PD-1/PD-L1 (Programmed death-ligand 1 and its receptor) . (nih.gov)
- CTLA-4 blockade plus Id2kd vaccination induces tumor specific T-cell expansion and tumor infiltration in mice, in which the infiltrating CD8 T cells are characterized by PD1 expression. (prolekare.cz)
- The recent development of therapies against immune checkpoint molecules, namely, CTLA-4, PD-1 and PD-L1 has shown that PD-1/PD-L1 blockade can improve overall survival in patients with cancer including malignant melanoma, lung squamous cell carcinoma, and lung adenocarcinoma ( 6 - 13 ). (iiarjournals.org)
- However, the susceptibility to blockade of PD1 signaling varied between individuals and PD1 blockade alone was not able to restore function of intrahepatic HCV-specific CD8+ T cells  . (prolekare.cz)
- Placement of the DNR transgene under the control of the CD11c promoter (CD11cdnTGF-RII) results in a specific TGF-β signaling blockade in innate immune cells ( 36 ), while CD4 promoter control (CD4dnTGF-RII) leads to TGF-β signaling inhibition in CD4 + and CD8 + T cells ( 27 ). (asm.org)
- Programmed death 1 (PD-1) receptor blockade is active in classic Hodgkin lymphoma (cHL) despite reported deficiencies of major histocompatibility complex (MHC) class I expression on HRS cells. (elsevier.com)
- Herein, we assess bases of sensitivity to PD-1 blockade in patients with relapsed/refractory cHL who were treated with nivolumab (anti-PD-1) in the CheckMate 205 trial. (elsevier.com)
- These parameters were correlated with clinical responses and progression-free survival (PFS) after PD-1 blockade. (elsevier.com)
- Conclusion Genetically driven PD-L1 expression and MHC class II positivity on HRS cells are potential predictors of favorable outcome after PD-1 blockade. (elsevier.com)
- Recently, PD-1/PD-L1 blockade has emerged as a therapeutic strategy for patients with cancer [ 2 ], and has been approved for the first-line and second-line treatment of patients with non-small-cell lung cancer (NSCLC) [ 3 ]. (biomedcentral.com)
- Although immunohistochemistry for PD-L1 has been approved as a companion/complementary diagnostics for PD-1/PD-L1 blockade, the response rate to PD-1/PD-L1 blockades is approximately 30% even in patients with PD-L1 positive NSCLC [ 5 ]. (biomedcentral.com)
- Thus, more studies are needed to understand the biology and the mechanism of action of PD-1/PD-L1 blockade. (biomedcentral.com)
- This over-expression makes Hodgkin lymphoma uniquely vulnerable to PD-L1 blockade, as it appears that Hodgkin lymphoma cells depend on this mechanism to survive. (cancerworld.net)
- Here, we performed a study of PD-1 or PDL-1 blockade in combination with reference chemotherapies in four fully immunocompetent mouse models of cancer. (bxcell.com)
- PD-1 blockade induces responses by inhibiting adaptive immune resistance. (b-t.cr)
- CTLA4 blockade broadens the peripheral T-cell receptor repertoire. (b-t.cr)
- Exciting stuff, but I don't see how TCR sequencing before PD-1 blockade can predict the response and therefore it is hard to use it as a biomarker. (b-t.cr)
- Binding of programmed death ligands to their cognate receptor, programmed death 1 (PD-1), on T cells results in a blockade of downstream T cell receptor signaling inducing anergy, exhaustion, and apoptosis in inflammatory effector T (Teff) cells (2), while stimulating de novo differentiation and existing pool expansion of regulatory T (Treg) cells (3,4). (docme.ru)
- Blockade of PD-1/PD-L1 interactions dramatically improves the function of osteosarcomareactive CTLs in vitro and in vivo, and results in decreased tumor burden and increased survival in the K7M2 mouse model of metastatic osteosarcoma. (elsevier.com)
- Our results suggest that blockade of PD-1/PD-L1 interactions in patients with metastatic osteosarcoma should be pursued as a therapeutic strategy. (elsevier.com)
- Our data extend the current knowledge on Betaherpesviral evasion from T cell immunity and show for the first time that, beyond impaired antigen presentation, infected cells are efficiently protected by direct blockade of cytotoxic effector functions through viral proteins. (pubmedcentralcanada.ca)
Effector T cel7
- Several studies have shown that the death of the majority of activated T cells responding to a foreign Ag in vivo can be prevented by enforced expression of Bcl-2, indicating that Bcl-2 up-regulation in effector T cells plays a critical role in preventing activated T cell death by ACAD during the contraction phase ( 10 , 11 , 14 ). (jimmunol.org)
- Expression of PD-L1 on tumor cells inhibits anti-tumor activity through engagement of PD-1 on effector T cells. (wikipedia.org)
- PDA is distinguished by a dense desmoplastic stroma, rich in fibroblasts, extracellular matrix, and inflammatory leukocytes (but few infiltrating effector T cells). (aacrjournals.org)
- upregulate inhibitory receptors and molecules that hinder effector T-cells. (1library.net)
- During chronic HBV infection, naive T cells are primed by antigens and then differentiate into effector T cells. (biomedcentral.com)
- Unless the infection is cleared following antigen clearance, and the intrahepatic inflammation is diminished or substantially reduced, partially functional effector T cells can further differentiate into highly polyfunctional memory T cells. (biomedcentral.com)
- Additionally, "off-the-shelf" novel dual targeting antibody strategies are being developed that engage both the myeloma cell and effector T cells. (cancernetwork.com)
- Pembrolizumab (MK-3475) is a potent, highly selective, IgG4-κ humanized monoclonal antibody that prevents PD-1 binding with its ligands, PD-L1 and PD-L2. (aacrjournals.org)
- Binding of PD-1 to either PD-L1 or PD-L2 results in the activation of inhibitory kinases involved in T-cell proliferation, adhesion, and cytokine production/secretion via phosphatase SHP2.2 PD-1-PD-L interaction has been shown to play an important role in limiting the initial response of T cells upon antigen exposure and inducing T-cell tolerance. (thefreelibrary.com)
- Moreover, JP-1 activates AMPK α and reduces mTOR activity, implying its inhibitory effect on the energy-sensitive protein synthesis and cell proliferation signaling. (hindawi.com)
- Our results show that JP-1 activates p53/miR-34a tumor suppressor axis and decreases proteins related to proliferation, apoptosis resistance, and metastasis, suggesting its potential as a complementary medicine for LADC treatment. (hindawi.com)
- Binding of PD-L1 to its receptors suppresses T-cell migration, proliferation and secretion of cytotoxic mediators, and restricts tumour cell killing. (nih.gov)
- By inhibiting TCR signaling, PD-1 prevents the activation of the PI3K/Akt and c-Myc pathways, and inhibits cell survival, proliferation, and cytokine production by CD8 + T cells ( 8 ). (frontiersin.org)
- Using mixed leukocyte reaction it was observed that the de-fucosylated anti-PD-L1 antibody induced the strongest CD8 T cell activation determined by expression of activation markers, proliferation, and cytotoxicity against cancer cells. (frontiersin.org)
- Engagement of PD-1 on T cells by PD-L1 leads to their functional suppression evident by decreased cytokine production and proliferation ( 3 ). (frontiersin.org)
- T-cell proliferation and IFN-γ secretion served as measures of T-cell activation. (aacrjournals.org)
- Anti-PD-L1 blocking antibody boosted proliferation and IFN-γ secretion by allogeneic T cells responding to ALCL and DLBCL cells. (aacrjournals.org)
- Programmed death 1 (PD-1), a member of the CD28 family, is an inhibitory receptor expressed on the surface of T cells that functions to physiologically limit T-cell activation and proliferation ( 1 ). (aacrjournals.org)
- The fraction of tumor-infiltrating Teffs expressing CTLA-4 and PD-1 increases, reflecting the proliferation and accumulation of cells that would otherwise be anergized. (pnas.org)
- Once mobilized, however, T cells begin to express other members of the CD28/B7 receptor family that attenuate the immune response through inhibition of proliferation and cytokine production ( 2 ). (pnas.org)
- Besides viral escape mutations HCV-specific CD8+ T cells are functionally impaired and lack key effector functions such as cytokine production, proliferation and cytotoxicity  ,  . (prolekare.cz)
- Promotes T-Cell proliferation (esp. (fpnotebook.com)
- Transforming growth factor β (TGF-β) is a pleiotropic cytokine that is present on most cell types and acts as a switch to regulate processes such as immune function, cell proliferation, and differentiation ( 14 , 67 , 68 ). (asm.org)
- For example, if undesired cells could be induced to alter their behavior to undergo apoptosis while normal cells retain normal function, subjects with a disease caused by proliferation of undesired cells would obtain relief from the disease. (google.com)
- Some studies have shown that proteins in ECM that are nonstructural matrix proteins, such as heparan sulfate proteoglycans (HSPGs), have a major role in the maintenance of tumor cell proliferation and migration. (biomedcentral.com)
- In vitro, treatment of anti-CD3 stimulated T cells with PD-L1-Ig results in reduced T cell proliferation and IFN-γ secretion. (wikipedia.org)
- Reduced T cell proliferation was also correlated with attenuated IL-2 secretion and together, these data suggest that PD-1 negatively regulates T cell responses. (wikipedia.org)
- To meet the metabolic requirements for growth and proliferation, tumor cells predominantly use glucose through aerobic glycolysis rather than oxidative phosphorylation (metabolic reprogramming known as the "Warburg effect") [ 10 ]. (biomedcentral.com)
- Engagement of PD-L1 with PD-1 leads to inhibition of TCR-mediated T cell proliferation and cytokine production. (bxcell.com)
- A soluble VISTA-Ig fusion protein or VISTA expression on APCs inhibits T cell proliferation and cytokine production in vitro. (rupress.org)
- and T-cell proliferation, adoptive transfer, and islet transplantation were performed to evaluate the PD-L1 transgene-mediated immune-protective mechanisms. (diabetesjournals.org)
- Although accumulating data indicate that both PD-L1/PD-1 and PD-L2/PD-1 signals can suppress T-cell proliferation and effector function by blocking cell cycle progression and cytokine production, signaling through PD-L1 interaction is more potent than that through PD-L2 ( 8 ). (diabetesjournals.org)
- Recent studies reveal Tfh cells are a separate subset of CD4 + T cells that are mainly responsible for promoting B cells to undergo proliferation, isotype switching and antibody response [ 3 - 5 ]. (biomedcentral.com)
- Surprisingly, we have found that TNBC proliferation requires PD-L1 and a subset of PD-L1 localizes in the nucleus and interacts with cohesin, a protein complex that is important for appropriate chromosome alignment and segregation during the cell cycle. (elsevier.com)
- Knocking down PD-L1 dramatically causes incomplete chromosome segregation and inhibits TNBC cell proliferation, while has no effect on normal cells. (elsevier.com)
- We propose to test this central hypothesis in the following Specific Aims: Aim 1, Determine the role of PD-L1 in regulation of cell cycle, genomic stability, and tumor cell proliferation by studying the exact mechanisms by which nuclear PD-L1 might regulate cohesion. (elsevier.com)
- PD-L1 also interferes with priming of naïve T cells (6), with polarization of CD4+ T cells towards TH1 subtype (3), with Teff cell proliferation (3,6), or it simply acts to reduce time of interaction between cytotoxic T lymphocytes (CTLs) and target cells, essentially acting as a shield to protect the latter against T cell-mediated immune responses (7). (docme.ru)
- Greater PDL1 surface expression in tumors or tumorassociated macrophages (TAMs) has been linked to poor prognosis and increased proliferation, epithelial-mesenchymal 2 Downloaded from http://www.jbc.org/ by guest on October 26, 2017 PD-L1 (programmed death ligand 1) and PDL2 are cell surface glycoproteins that interact with programmed death 1 (PD-1) on T cells to attenuate inflammation. (docme.ru)
- Blockage of the interaction of PD-1 and one of it's ligands, B7 homolog 1 (B7.H1), partially recovered proliferation and IFNγ production in both CD4+ and CD8+ T cells. (iastate.edu)
- Focal adhesion kinase (FAK) is definitely a cytoplasmic tyrosine kinase that plays a fundamental role in integrin and growth factor mediated signalling and is definitely an important player in cell migration and proliferation, processes vital for angiogenesis. (bostonscienceandengineeringlectures.com)
- In an RNAi‐based screening experiment, we identified dendritic arbor reduction 1 (Dar1), which is a KLF member in Drosophila, that inhibited the proliferation of intestinal stem cells (ISCs). (usda.gov)
- 8] EBV likely plays a role in the pathogenesis of this cancer, affecting cellular proliferation and the microenvironment, including the expression of programmed death ligand 1 on the malignant cells. (cancernetwork.com)
- To gain insight into these responses, we studied the interaction between PD-1 expressed on T cells and its ligands (PD-1:PD-L1, PD-1:PD-L2, and PD-L1:B7.1), expressed on other cells in the tumor microenvironment, using a syngeneic orthotopic mouse model of epithelial ovarian cancer (ID8). (aacrjournals.org)
- Another major category of signals that regulate the activation of T cells comes from soluble cytokines in the microenvironment. (nih.gov)
- Myeloid-derived suppressor cells (MDSCs) populating the tumor microenvironment can express both B7-1 and PD-L1 ( 4 ). (pnas.org)
- It has been proposed that four different types of tumor microenvironment exist based on the presence or absence of tumor-infiltrating lymphocytes and programmed death-ligand 1 (PD-L1) expression. (aacrjournals.org)
- The aim of immunostimulatory gene therapy is to tilt the suppressive tumor microenvironment to promote anti-tumor immunity. (nih.gov)
- The tumor microenvironment consists of both tumor cells and other cell types such as immature myeloid-derived suppressor cells (MDSC), M2 macrophages and T regulatory cells (Treg). (nih.gov)
- Unfortunately, the tumor and its microenvironment counteract immune responses by inducing immunosuppressive cells like M2 macrophages, myeloid-derived suppressor cells (MDSCs) and T regulatory cells (Tregs) [2,3] (Figure 1). (nih.gov)
- Objective The goal of this study was to determine the effect of myeloid cell depletion on the onset and progression of pancreatic cancer and to understand the relationship between myeloid cells and T cell-mediated immunity within the pancreatic cancer microenvironment. (bmj.com)
- We characterize the current state of CAR-modified T cell therapy and summarize the various strategies to combat the immunosuppressive microenvironment of solid tumors, with the aim of promoting T cell cytotoxicity and enhancing tumor cell eradication. (biomedcentral.com)
- Theoretically, modified-T cells have poor homing ability to tumor sites, and a hostile tumor-microenvironment (TME) containing many immunosuppressive cells and other inhibitory factors impairs migrated CAR-T cell cytotoxicity. (biomedcentral.com)
- Thus, they could compete for restricted nutrients within the tumor microenvironment (TME) and increased nutrient consumption by tumor cells could lead to an immunosuppressive TME by dampening the T-cell metabolism. (biomedcentral.com)
- Of the 204 patients, 100 (49.0%) were PD-L1-positive in tumor cells and 44 (21.6%) were PD-L1-positive in tumor microenvironment. (biomedcentral.com)
- PD-L1 expression in tumor cells and tumor microenvironment were more common in the non-germinal center B-cell-like (GCB) subtype than in the GCB subtype ( P = 0.02 and P = 0.04). (biomedcentral.com)
- We found that the balance between effector cells and immunosuppressive cells in the tumor microenvironment could be altered with some treatment combinations, but this effect was not always correlated with an impact on in vivo tumor growth. (bxcell.com)
- Conclusions Tumour CD274 expression is inversely associated with FOXP3 + cell density in colorectal cancer tissue, suggesting a possible influence of CD274-expressing carcinoma cells on regulatory T cells in the tumour microenvironment. (elsevier.com)
- The chronicity of HBV infection depends on viral factors, host immunity, and the intrahepatic microenvironment. (biomedcentral.com)
- Pathologic findings include angiodestruction, necrosis, and ulcers, with the malignant cells embedded in an inflammatory microenvironment. (cancernetwork.com)
- However, there are differences between PDL1 and PD-L2.2 PD-L1 is broadly expressed on many immune cell types, such as T cells, (9) B cells, macrophages, regulatory T (Treg) cells, and dendritic cells, as well as some non-immune cell types, such as vascular endothelial cells and pancreatic cells. (thefreelibrary.com)
- On the contrary, PD-L2 is largely limited to antigen-presenting cells, such as macrophages and dendritic cells. (thefreelibrary.com)
- Exhaustion of tumor-infiltrating lymphocytes (TIL) correlated with expression of PD-1 ligands by tumor cells and tumor-derived myeloid cells, including tumor-associated macrophages (TAM), dendritic cells, and myeloid-derived suppressor cells (MDSC). (aacrjournals.org)
- The programmed cell death-1 (PD-1) is an inhibitory surface receptor expressed by T cells, B cells, natural killer T cells, monocytes, and dendritic cells (DC), but not by resting T cells. (aacrjournals.org)
- These responses can occur at the initiation of T cell responses in lymph nodes (where the major APCs are dendritic cells) or in peripheral tissues or tumours (where effector responses are regulated). (nih.gov)
- Programmed death-ligand 1 (PD-L1, also referred to as B7-H1 or CD274) is constitutively expressed by cells of the myeloid lineage, including macrophages and dendritic cells ( 1 - 3 ). (frontiersin.org)
- The aim of immunostimulatory gene therapy is to shift the ongoing immunosuppression towards Th1 immunity by activating dendritic cells (DCs), T helper (Th)-1 cells and cytotoxic T lymphocytes (CTLs) to induce tumor-specific killing by lymphocytes. (nih.gov)
- Here, we show that the interaction between programmed cell death 1 ligand 1 (PD‐L1) on dendritic cells (DCs) and programmed death 1 (PD‐1) on CD8 T cells contributes to ligand‐induced TCR down‐modulation. (embopress.org)
- This process limits TCR signal transduction and prevents T cell hyperactivation after antigen‐presentation by dendritic cells. (embopress.org)
- We show here that binding of PD‐L1 on dendritic cells to PD‐1 on T cells is implicated in ligand‐induced TCR down‐modulation, by promoting Cbl‐b E3 ubiquitin ligase expression. (embopress.org)
- By combining PD‐L1 silencing with modulators of selected signalling pathways (MAPKs) in dendritic cells, we have increased their anti‐tumour activities, obtaining therapeutic effects with doses 100‐to‐1000‐fold lower than those currently used in experimental cancer models and in human clinical trials. (embopress.org)
- Vasoactive intestinal peptide (VIP) induces regulatory dendritic cells (DC) in vitro that inhibit cellular immune responses. (jimmunol.org)
- T cells and dendritic cells (DC) express VPAC1 and VPAC2, but not PAC1 ( 1 ). (jimmunol.org)
- Intratumoral administration of an immune primer is a therapeutic vaccine strategy aimed to trigger dendritic cell (DC)-mediated cross-presentation of cell-associated tumor antigens to cytotoxic CD8 + T cells without the need for tumor antigen characterization. (springer.com)
- Using Batf3 −/− mice, which are defective for cross-presentation of cell-associated antigens, we show that BATF3-dependent dendritic cells (DC) are essential for the response to therapy with anti-CD137 or anti-PD-1 mAbs. (aacrjournals.org)
- PD-L1 protein is upregulated on macrophages and dendritic cells (DC) in response to LPS and GM-CSF treatment, and on T cells and B cells upon TCR and B cell receptor signaling, whereas in resting mice, PD-L1 mRNA can be detected in the heart, lung, thymus, spleen, and kidney. (wikipedia.org)
- PD-L1 is expressed on T lymphocytes, B lymphocytes, NK cells, dendritic cells, as well as IFNγ stimulated monocytes, epithelial cells and endothelial cells. (bxcell.com)
- Murine PD-L1 is expressed on many cell types, including stromal cells within many organs, but PD-L2 expression is much more restricted, occurring mainly in dendritic cells, activated monocytes, and macrophages ( 6 , 7 ). (diabetesjournals.org)
- Given that HIV is a blood-borne pathogen, a number of cell types have been proposed to be the sites of latency, including resting memory CD4 + T cells, peripheral blood monocytes, dendritic cells and macrophages in the lymph nodes, and haematopoietic stem cells in the bone marrow. (biomedcentral.com)
- This review updates the latest advances in the study of HIV interactions with monocytes and dendritic cells, and highlights the potential role of these cells as viral reservoirs and the effects of the HIV-host-cell interactions on viral pathogenesis. (biomedcentral.com)
- Activated plasmacytoid dendritic cells regulate type 2 innate lymphoid cell-mediated airway hyperreactivityJ Allergy Clin Immunol. (usc.edu)
- Multiple platforms have been evaluated and are under investigation, including peptide-based vaccines and cellular vaccination strategies using dendritic cells. (cancernetwork.com)
- Activation of calreticulin-mediated signaling by the SE ligand in mouse dendritic cells (DC) was found to lead to polarization of T helper cells towards TH17 cells . (scirp.org)
- These IFNs directly enhance dendritic cell and CD8 + T cell activity. (jci.org)
- These trials further demonstrate the efficacy of PD-1/PD-L1-targeted therapy and reveal the new era of cancer immunotherapy. (thefreelibrary.com)
- Overexpression of PD-L1 in murine tumor models results in inhibition of T-cell-mediated immune response via the PD-L1/PD-1 axis, indicating that blocking this axis has an important role in immunotherapy against cancers. (thefreelibrary.com)
- Overall, we present data based on samples obtained from women with ovarian cancer, suggesting the PD-1 pathway may be used as a reliable diagnostic marker in OC, as well as a viable target for use with PD-1/PD-L1-directed antibody immunotherapy. (springer.com)
- Three phase 1/2 drug trials are ongoing involving treatment of PDACs with immunotherapy (NCT02583477, NCT02305186, NCT02452424). (biomedcentral.com)
- Hypoxia influences efficacy of immunotherapy via several mechanisms, including both innate and adaptive immunity. (jci.org)
- In this trial, 18 F-HX4 PET is used to guide tumor biopsies of hypoxic and normoxic regions for assessment of T cell infiltrate and effector function before and after immunotherapy. (jci.org)
- Furthermore, the field of cancer immunotherapy has experienced a resurgence in recent years, due in part to the remarkable clinical efficacy observed with immune checkpoint inhibitors against a number of cancer types such as melanoma, renal cell carcinoma, bladder cancer, non-small cell lung carcinoma (NSCLC), and Hodgkin disease ( 9-13 ). (aacrjournals.org)
- In experimental settings, many immunotherapies have been evaluated, but real success has been absent until the patients were preconditioned with chemotherapy and/or irradiation to remove some of the immunosuppressive cells prior to immunotherapy. (nih.gov)
- 4 IBP-UTSW Joint Immunotherapy Group, Chinese Academy of Science Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. (sciencemag.org)
- We herein show that orchiectomy synergizes with immunotherapy, whereas the more widely used treatment of medical ADT involving androgen receptor (AR) antagonists suppresses immunotherapy. (sciencemag.org)
- 1 Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, and Instituto de Investigación Sanitaria de Navarra (IdISNA), Pamplona, Spain. (aacrjournals.org)
- The potential for adoptive cell immunotherapy as a treatment against cancers has been demonstrated by the remarkable response in some patients with hematological malignancies using autologous T cells endowed with chimeric antigen receptors (CARs) specific for CD19. (biomedcentral.com)
- Cancer immunotherapy Chimeric antigen receptor Pardoll DM (March 2012). (wikipedia.org)
- In the advent of Immune Checkpoint inhibitors (ICI) and of CAR-T adoptive T-cells, the new frontier in Oncology is Cancer Immunotherapy because of its ability to provide long term clinical benefit in metastati. (biomedcentral.com)
- Immunotherapy drugs called checkpoint inhibitors inhibit either the PD-1 checkpoint or PD-L1 to lift those brakes so the immune system can go after the tumor. (egfrcancer.org)
- Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. (b-t.cr)
- This study provides evidence associated with anti-PD-1 immunotherapy against TNBC tumors supporting the use of TNBC PDXs in humanized mice as a model to overcome some of the technical difficulties associated with the preclinical investigation of immune-based therapies. (biomedcentral.com)
- Cancer immunotherapy has witnessed a revolution in the past decade with the development of immune checkpoint inhibitors (ICIs), monoclonal antibodies against cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) or their ligands, such as PD1 ligand 1 (PD-L1). (biomedcentral.com)
- Siglecs are expressed at very low levels on normal T cells, and these receptors were not until recently considered as interesting targets on T cells for cancer immunotherapy. (jci.org)
- Our data identify the sialoglycan-SAMP/Siglec pathway as a potential target for improving T cell activation for immunotherapy. (jci.org)
- While these factors have limited its generalized use, high-dose IL-2 serves as proof of principle that immunotherapies can eliminate tumor cells in some patients, encouraging efforts to develop better tolerated and more effective immunotherapy regimens. (biomedcentral.com)
- PD-1, a cell surface protein belonging to the CD28 family, is encoded by PDCD1 gene located in chromosome 2q37.2 PD-1 is expressed on activated T cells, with particularly high expression by tumor-infiltrating T lymphocytes. (thefreelibrary.com)
- In general, pairs of co-stimulatory-inhibitory receptors that bind the same ligand or ligands - such as CD28 and cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) - display distinct kinetics of expression with the co-stimulatory receptor expressed on naive and resting T cells, but the inhibitory receptor is commonly upregulated after T cell activation. (nih.gov)
- Upon interaction with PD-L1, PD-1 counteracts signaling downstream of T cell receptor (TCR) ligation and CD28 co-stimulation ( 6 ). (frontiersin.org)
- PD-1, the receptor of PD-L1, is a member of the CD28 family expressed on activated T cells ( 4 ). (frontiersin.org)
- Binding of PD-L1 to its receptor inhibits T-cell activation and counterbalances T-cell stimulatory signals, such as the binding of B7 to CD28. (aacrjournals.org)
- In addition to TCR activation, costimulation via ligation of the coreceptor CD28 on T cells by B7 molecules on antigen-presenting cells (APCs) is required for optimal T-cell activation ( 1 ). (pnas.org)
- Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is rapidly up-regulated following T-cell activation and binds to B7 molecules with a higher affinity than does CD28. (pnas.org)
- T reg cells are also essential for the maintenance of peripheral tolerance, and roles for B7-CD28 family members during T reg cell development are emerging. (rupress.org)
- PD-1 is a member of the extended CD28/CTLA-4 family of T cell regulators. (wikipedia.org)
- CD28 is expressed by naive and activated T cells and is critical for optimal T cell activation. (rupress.org)
- In contrast, CTLA-4 is induced upon T cell activation and inhibits T cell activation by binding to B7.1/B7.2, impairing CD28-mediated co-stimulation. (rupress.org)
- Accordingly, additional CD28 family receptors have been identified. (rupress.org)
- Programmed death 1 (PD-1) is an immunoreceptor of the CD28/CTLA-4 family whose expression is induced in activated T- and B-cells and in macrophages ( 1 , 2 ). (diabetesjournals.org)
- Initial antigen-mediated activation of T cells is modulated by several regulatory mechanisms, including engagement co-stimulatory signals like the binding of CD28 on T cells to CD80/B7-1 and/or CD86/B7-2 on antigen-presenting cells. (biomedcentral.com)
- By outcompeting CD28 for binding to B7.1 and B7.2, CTLA-4 can prevent the co-stimulation necessary to generate and maintain T cell activation. (biomedcentral.com)
- PD-L1 is expressed in several solid tumors, including melanoma, glioblastoma, lung cancer, renal cancer, gastric cancer, colorectal cancer, pancreatic cancer, breast cancer, and cervical and ovarian cancers (please see Table 1 for percentage of PD-L1 expression in various tumors). (thefreelibrary.com)
- Flow cytometric analysis of T cells present in the ascites and blood showed a correlation of PD-1 expression with malignant tumors versus benign/borderline, in a similar manner to PD-L1 expression on monocytes. (springer.com)
- Tumors can use the PD-1 inhibitory pathway to silence the immune system ( 8 ). (aacrjournals.org)
- In ovarian tumors, myeloid cells are one of the major determinants of immune suppression. (aacrjournals.org)
- CD47 is an antiphagocytic ligand expressed by tumors that binds the inhibitory receptor signal regulatory protein alpha (SIRPα) on phagocytic cells. (pnas.org)
- Ample evidence now exists that T cells infiltrating tumors can be inhibited by both CTLA-4 and PD-1 coinhibitory signals. (pnas.org)
- In addition, tumors themselves sometimes express PD-L1, which can negatively signal T cells through both the PD-1 and B7-1 molecules on their surface ( 5 ). (pnas.org)
- In tumors, there are all types of immune cells that can have various effects on tumor progression, and a spectrum of soluble cytokines and chemokines that regulates the entry of different types of infiltrating immune cells. (aacrjournals.org)
- We recently reported that Id2 knockdown of mouse neuroblastoma (Id2kd-N2a) cells are rejected by most mice following inoculation and that the same mice then fail to grow tumors when subsequently rechallenged with wild-type Neuro2a cells. (prolekare.cz)
- Antibody depletion of CD8 + cells or immune-incompetent mice grow Id2kd tumors avidly, validating the concept that Id2 knockdown confers tumor cell immunogenicity in immune-competent hosts. (prolekare.cz)
- Acting in concert with a costimulatory CTLA-4 checkpoint inhibitor, Id2kd-N2a whole tumor cell vaccination generated a potent tumor-specific T-cell response, capable of eradicating established tumors in 60% of mice [ 13 , 14 ]. (prolekare.cz)
- The combination of Id2kd-N2a cell vaccination with anti CTLA-4 plus anti PD-L1 antibody treatment proved to be highly effective, even against established neuroblastoma tumors, resulting in cure of treated mice ( n = 16) as well as long-term immune memory (6 months). (prolekare.cz)
- Characteristically, tumor infiltration of T cells and PD-L1 expression seem to also be associated with risk stratification in human neuroblastoma tumors. (prolekare.cz)
- Low- and intermediate-risk tumors have abundant infiltrating T cells that are surrounded with high PD-L1 tumor expression, while high-risk tumors lack significant T-cell infiltrates and PD-L1 expression. (prolekare.cz)
- Bladder cancer is a highly immunogenic malignancy, including T cell-inflamed and non-T cell-inflamed tumors [ 1 ]. (oncotarget.com)
- Clinical efficacy of CAR-T cell therapy for the treatment of solid tumors, however, is rare due to physical and biochemical factors. (biomedcentral.com)
- Although CAR-T cell treatment of solid tumors has not shown promising response, a comprehensive understanding of the multiple barriers seen in the TME is necessary to advance CAR engineering in cancer immunology. (biomedcentral.com)
- In this review, we analyze the factors that limit the application of CAR-T cell therapy in the treatment of solid tumors. (biomedcentral.com)
- It has become clear that these cells and released cytokines, such as transforming growth factor-β (TGF-β) and interleukin (IL) 10, inside solid tumors seriously dampen the efficacy of infused CAR-T cells. (biomedcentral.com)
- PD-1 inhibitors, a new class of drugs that block PD-1, activate the immune system to attack tumors and are used to treat certain types of cancer. (wikipedia.org)
- Consistently, there were fewer CD8 + T-cells in PD-L1 positive /HK2 high tumors compared to PD-L1 positive /HK2 low tumors in squamous cell carcinoma. (biomedcentral.com)
- Tumor T cells expressed PD-1 as prominently as T cells from chronically infected mice, but treatment with αPD-1 mAbs, with or without αCTLA-4 mAbs, failed in well-established tumors, recapitulating clinical results. (aacrjournals.org)
- Agonist αCD40 mAbs with chemotherapy induced T-cell immunity and reversed the complete resistance of pancreatic tumors to αPD-1 and αCTLA-4. (aacrjournals.org)
- The combination of αCD40/chemotherapy plus αPD-1 and/or αCTLA-4 induced regression of subcutaneous tumors, improved overall survival, and conferred curative protection from multiple tumor rechallenges, consistent with immune memory not otherwise achievable. (aacrjournals.org)
- examined the genomic features of tumors from patients with metastatic renal cell carcinoma who had been treated with immune checkpoint inhibitors. (sciencemag.org)
- Spartalizumab (PDR001) is a PD-1 inhibitor being developed by Novartis to treat both solid tumors and lymphomas. (wikipedia.org)
- Induced PD-L1 expression is common in many tumors and results in increased resistance of tumor cells to CD8 T cell mediated lysis. (bxcell.com)
- One of the main mechanisms by which the tumors evade the immune system is activation of the PD-1 pathway, which causes exhaustion of the T cells that are responsible for killing cancer cells," explains Suresh S. Ramalingam, M.D., assistant dean for cancer research and deputy director of the Winship Cancer Institute at Emory University School of Medicine in Atlanta. (egfrcancer.org)
- Keytruda (pembrolizumab) was the first PD-1 checkpoint inhibitor approved by the FDA for first-line treatment of lung cancer in patients whose tumors have high expression of PD-L1, which is approximately 25 to 30 percent of patients with NSCLC. (egfrcancer.org)
- Human CD45 + , CD20 + , CD3 + , CD8 + , CD56 + , CD68 + , and CD33 + cells were readily identified in blood, spleen, and bone marrow collected from hNSG, as well as human cytokines in blood and engrafted tumors. (biomedcentral.com)
- Engineering Chimeric Antigen Receptor T-Cells for Racing in Solid Tumors: Don't Forget the Fuel. (1library.net)
- We show that human metastatic, but not primary, osteosarcoma tumors express a ligand for PD-1 (PD-L1) and that tumor-infiltrating CTLs express PD-1, suggesting this pathway may limit CTLs control of metastatic osteosarcoma in patients. (elsevier.com)
- CD4 + and CD8 + T lymphocytes comprise primary effector cells against tumors. (biomedcentral.com)
- Pronounced immune responses were provoked after ionizing radiation of tumors from 4 mouse cancer cell lines with Ifnar1 knockout. (jci.org)
- PD-1 binds two ligands, programmed cell death ligand 1 (PD-L1) and PD-L2 called B7-H1 and B7-DC, respectively ( 8, 9 ). (aacrjournals.org)
- Once it is expressed on the tumor cells, PD-L1 binds to its receptor, PD-1, on the membrane of the cytotoxic T cell and inhibits T cell activity, resulting in the escape of the tumor cell from the immune system ( 5 ). (iiarjournals.org)
- PAC1 is mainly expressed on neuron and endocrine cells in the brain and pituitary and adrenal glands, and selectively binds PACAP ( 7 ). (jimmunol.org)
- PD-1 binds two ligands, PD-L1 and PD-L2. (wikipedia.org)
- GPR55 is an unique orphan G-receptor which binds to cannabinoids. (bvsalud.org)
- PD-L1 on the cell surface binds to PD-1 on an immune cell surface, which inhibits immune cell activity. (wikipedia.org)
- It binds to T cell receptors, thereby inhibiting T-cell-mediated immunity. (cancerworld.net)
- PD-L1 binds to its receptor, PD-1, found on CD4 and CD8 thymocytes as well as activated T and B lymphocytes and myeloid cells. (bxcell.com)
- Upon administration, anti-PD-1 monoclonal antibody ABBV-181 targets and binds to PD-1, thereby blocking its binding to the PD-1 ligand, programmed cell death-1 ligand 1 (PD-L1), and preventing the activation of PD-1/PD-L1 downstream signaling pathways. (cancer.gov)
- Nivolumab binds to and blocks the activation of PD-1, an Ig superfamily transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs. (cancer.gov)
- CTLA-4 is a receptor exclusively expressed on T cells that binds to CD80 (B7.1) and CD86 (B7.2) on antigen-presenting cells [ 11 ]. (biomedcentral.com)
- Treatment with JP-1 induces p53 and its downstream p21 and BAX proteins as well as the miR-34a, resulting in growth inhibition, colony formation reduction, migration repression, and apoptosis induction. (hindawi.com)
- Although there is significant overlap in PTI - and ETI -based responses, ETI typically induces a stronger response and culminates in programmed cell death at the site of infection ( Chiang and Coaker, 2015 ). (plantphysiol.org)
- We hypothesized that the DNA damage response in tumor cells induces an immune response, thereby up-regulating programmed death-ligand 1 (PD-L1) expression on tumor cells, which in turn sensitizes them to anti-PD-1 therapy. (iiarjournals.org)
- These results suggest that goniodomin A induces morphological change by increasing the content of filamentous actin in non-muscle cells. (faintpower.ga)
- Triggering PD-1, expressed on monocytes and up-regulated upon monocytes activation, by its ligand PD-L1 induces IL-10 production which inhibits CD4 T-cell function. (wikipedia.org)
- 11 . The method of claim 4 , wherein the member is mesenchymal stem cells further modified to express a molecule that induces activated T cell death. (google.com)
- We identified and characterized vitamin D response elements (VDREs) located in both genes and showed that 1,25D treatment induces cell surface expression of PD-L1 in epithelial and myeloid cells. (docme.ru)
- Subsequently, the body begins to fight inflammation in order to balance immunity status and eventually induces the immune paralysis or immunosuppressive state characterized by exhaustion of immune cell. (bvsalud.org)
- Co-ligation of TCR with PD-1 molecules induces an inhibitory signal in T cells characterized by cell cycle arrest, inability to proliferate and reduced cytokine synthesis (IFN-γ and/or IL-2). (biomedcentral.com)
- Gene engineered chimeric antigen receptor (CAR) T lymphocytes have also shown spectacular results in B cell malignancy after the introduction of preconditioning strategies . (nih.gov)
- approach is chimeric antigen receptor (CAR) T-cell therapy. (1library.net)
- In order to explore the potential of HLA-independent T cell therapy for human cytomegalovirus (HCMV) infections, we developed a chimeric antigen receptor (CAR) directed against the HCMV encoded glycoprotein B (gB), which is expressed at high levels on the surface of infected cells. (pubmedcentralcanada.ca)
- Therapy using chimeric antigen receptor T cells and T-cell receptor-transduced T cells are the two major strategies now under investigation. (cancernetwork.com)
- Chimeric antigen receptor T (CAR-T) cells are a promising new treatment for patients with relapsed or refractory hematologic malignancies, including lymphoma. (biomedcentral.com)
- One patient with melanoma and one with Merkel cell carcinoma experienced complete responses of 57 and 56+ weeks' duration, respectively. (aacrjournals.org)
- Here we show that across multiple cancer types, responses (as evaluated by Response Evaluation Criteria in Solid Tumours, version 1.1) were observed in patients with tumours expressing high levels of PD-L1, especially when PD-L1 was expressed by tumour-infiltrating immune cells. (nih.gov)
- Furthermore, responses were associated with T-helper type 1 (TH1) gene expression, CTLA4 expression and the absence of fractalkine (CX3CL1) in baseline tumour specimens. (nih.gov)
- Finally, we demonstrate functional links between PD-L1 expression on monocytes and OC tumor cells with suppression of T cell responses. (springer.com)
- Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses. (nih.gov)
- By expression of major histocompatibility complex (MHC) class II molecules and allergen-specific T-cell receptors (TCRs) they link innate and adoptive immune responses. (ersjournals.com)
- The tissue expression of PD-L1 is essentially involved in mediating peripheral T cell tolerance ( 5 ), whereas PD-L1 expression on APC is decisive for regulating T cell immune responses in lymphoid tissues ( 6 ). (frontiersin.org)
- Here, we describe the spectrum of expression of PD-L1 among non-Hodgkin lymphomas (NHL) and evaluate its functional activity in suppressing T-cell responses. (aacrjournals.org)
- Immune checkpoint receptors on immune cells, when engaged by their ligands, transmit an inhibitory signal, maintain self-tolerance, and regulate the duration and amplitude of immune responses in peripheral tissues to minimize tissue pathology ( 14 ). (aacrjournals.org)
- TCR repertoire analysis further suggests a role for specific T cell responses in hereditary versus idiopathic CP pathogenesis providing new insights into immune responses associated with human CP. (stanford.edu)
- Thus, PD-L1 can inhibit T cell responses by promoting both the induction and maintenance of iT reg cells. (rupress.org)
- The PD-1-PD-L1 pathway exerts its effects during the initial phase of activation and expansion of autoreactive T cells by attenuating self-reactive T cell responses during presentation of self-antigen by DCs. (rupress.org)
- Virus-specific CD8+ T cell responses generated during the early onset of HCV infection are strong and multispecific, however, in settings of persistent virus infections virus-specific T cells gradually become exhausted  ,  . (prolekare.cz)
- We tested the role of physiological levels of VIP on immune responses to murine CMV (mCMV) using VIP-knockout (VIP-KO) mice and radiation chimeras engrafted with syngenic VIP-KO hematopoietic cells. (jimmunol.org)
- Enhanced antiviral immunity was also seen in WT transplant recipients engrafted with VIP-KO hematopoietic cells, indicating that VIP synthesized by neuronal cells did not suppress immune responses. (jimmunol.org)
- In adaptive immune responses, VIP polarizes CD4 + T cells to an immunosuppressive Th2 response while suppressing the Th1 responses ( 9 ). (jimmunol.org)
- Furthermore, we observed that the use of medical ADT could unexpectedly impair the adaptive immune responses through interference with initial T cell priming rather than in the reactivation or expansion phases. (sciencemag.org)
- These findings strongly suggest that TGF-β signaling, which generally functions to dampen immune responses, results in increased HSV-1 latency. (asm.org)
- In cHL, clinical responses to nivolumab were not dependent on HRS cell expression of MHC class I. (elsevier.com)
- Tregs play an important role in the regulation of immune responses, including CD4 + CD25 + Tregs and type 1 Tregs. (biomedcentral.com)
- In 1999, the same group demonstrated that mice where PD-1 was knocked down were prone to autoimmune disease and hence concluded that PD-1 was a negative regulator of immune responses. (wikipedia.org)
- PD-1 is expressed on the surface of activated T cells, B cells, and macrophages, suggesting that compared to CTLA-4, PD-1 more broadly negatively regulates immune responses. (wikipedia.org)
- Several lines of evidence suggest that PD-1 and its ligands negatively regulate immune responses. (wikipedia.org)
- Consistent with a role in negatively regulating CD8+ T cell responses, using an LCMV viral vector model of chronic infection, Rafi Ahmed's group showed that the PD-1-PD-L1 interaction inhibits activation, expansion and acquisition of effector functions of virus specific CD8+ T cells, which can be reversed by blocking the PD-1-PD-L1 interaction. (wikipedia.org)
- The programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses. (biomedcentral.com)
- Specifically, MyD88 was first shown to be involved in type 1 interleukin-1 receptor (IL-1R1) signaling and subsequently in all TLRs (Hultmark 1994 ) signaling except for TLR3 responses and TLR4 -mediated late responses. (springer.com)
- A VISTA-specific monoclonal antibody interferes with VISTA-induced suppression of T cell responses by VISTA-expressing APCs in vitro. (rupress.org)
- These molecules provide not only a second signal for T cell activation but also a balanced network of positive and negative signals to maximize immune responses against infection while limiting immunity to self. (rupress.org)
- In contrast, PD-1 (programmed death 1) negatively regulates T cell responses. (rupress.org)
- In the clinic, blocking either PD‑1 or one of its principal counterligands, programmed death-ligand 1 (PD‑L1), can lead to dramatic responses in certain patients. (jci.org)
- OBJECTIVE -Coinhibitory signals mediated via programmed death 1 (PD-1) receptor play a critical role in downregulating immune responses and in maintaining peripheral tolerance. (diabetesjournals.org)
- Programmed death 1 ligand 1 (PD-L1), the interacting ligand for PD-1, widely expressed in many cell types, acts as a tissue-specific negative regulator of pathogenic T-cell responses. (diabetesjournals.org)
- We know they can work if we can block those immune checkpoints, because suboptimal T cells are the ones that are causing responses that we see in melanoma and non-small cell lung cancer and in some patients with triple-negative breast cancer," Dr. Disis noted. (ascopost.com)
- Although the extracellular role of PD-L1 in the regulation of T-cell responses has been well studied, potential intracellular functions of PD-L1 in cancer remain largely unknown. (elsevier.com)
- Similarly, vitamin D signaling has been increasingly investigated for its nonclassical actions in stimulation of innate immunity and suppression of inflammatory responses. (docme.ru)
- These findings reinforce the physiological role of 1,25D in controlling inflammatory immune responses, but may represent a doubleedged sword as they suggest that elevated vitamin D signaling in humans could suppress anti-tumor immunity. (docme.ru)
- These immune checkpoint molecules constitute a system of negative regulators involved in controlling T-cell responses. (biomedcentral.com)
- The aims of the present study were to investigate memory T cell status in patients with different outcomes following pegylated interferon-α (IFN-α) therapy and to identify new biomarkers for predicting antiviral immune responses. (biomedcentral.com)
- CD33-related sialic acid-binding immunoglobulin-like lectins (Siglecs) are pattern-recognition immune receptors binding to a range of sialoglycan ligands, which appear to function as self-associated molecular patterns (SAMPs) that suppress autoimmune responses. (jci.org)
- Our data thus reveal that the tissue parenchyma has the capability of suppressing T cell responses and limiting damage to self. (jci.org)
- This results in the activation of T-cells and cell-mediated immune responses against tumor cells or pathogens. (cancer.gov)
- We identified multiple receptor-like protein kinases changing in abundance, including cysteine (Cys)-rich receptor-like kinases (CRKs) that are up-regulated upon the perception of flagellin. (plantphysiol.org)
- CRK28-mediated cell death required the common receptor-like protein kinase coreceptor BAK1. (plantphysiol.org)
- PD-L1 (also known as CD274 or B7-H1), a B7 family member, is a transmembrane protein broadly expressed not only in hematopoietic cells, such as B and T lymphocytes and macrophages but also on nonhematopoietic cells ( 2 , 3 ). (frontiersin.org)
- CD47 is an antiphagocytic ligand exploited by tumor cells to blunt antibody effector functions by transmitting an inhibitory signal through its receptor signal regulatory protein alpha (SIRPα). (pnas.org)
- In the clinic, three immune checkpoint inhibitor antibodies have been approved by the U.S. FDA for the treatment of advanced melanoma, the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blocking antibody ipilimumab, and two antibodies blocking programmed death 1 (PD-1), pembrolizumab and nivolumab. (aacrjournals.org)
- CD244) is a transmembrane protein belonging to the Ig superfamily which can also be expressed by CD8+ T cells. (prolekare.cz)
- IL6 and YKL-40 (also known as chitinase 3-like 1 protein, CHI3L1) are produced by pancreatic cancer cells and macrophages and activate inflammation. (aacrjournals.org)
- C-reactive protein (CRP) is synthesized mainly in hepatic cells and primarily stimulated by IL6. (aacrjournals.org)
- We found that myeloid cells inhibited CD8 + T-cell anti-tumour activity by inducing the expression of programmed cell death-ligand 1 (PD-L1) in tumour cells in an epidermal growth factor receptor (EGFR)/mitogen-activated protein kinases (MAPK)-dependent manner. (bmj.com)
- Agents known as immune check point inhibitors (CPIs), particularly therapeutic antibodies that block the immunosuppressive programmed cell death protein-1 (PD-1) and the programmed cell death-ligand 1 (PD-L1) pathway, are now revolutionizing the practice of medical oncology due to their ability to improve outcomes in various malignancies. (springer.com)
- Programmed cell death protein 1, also known as PD-1 and CD279 (cluster of differentiation 279), is a protein on the surface of cells that has a role in regulating the immune system's response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity. (wikipedia.org)
- The PD-1 protein in humans is encoded by the PDCD1 gene. (wikipedia.org)
- PD-1 is a type I membrane protein of 288 amino acids. (wikipedia.org)
- We discovered that one class of skin cells, the fibroblasts, encode the positional identity of skin via specific markings on their chromatin, the DNA-protein complex where genes reside. (stanford.edu)
- RESULTS: Calcium-mediated degradation of Src decreased survival signaling via phosphoinositide 3-kinase and protein kinase B and resulted in significant inhibition of the clonogenic ability of hormone-dependent breast cancer cells. (bvsalud.org)
- EBNA3C can also circumvent autophagy-lysosomal mediated protein degradation and subsequent antigen presentation for T-cell recognition. (bvsalud.org)
- PD-1 is the transmembrane programmed cell death 1 protein (also called PDCD1 and CD279), which interacts with PD-L1 (PD-1 ligand 1, or CD274). (wikipedia.org)
- MyD88 is a 296 amino acid cytoplasmic adaptor protein that relays signals from IL-1, IL-18, IFNγ, IL-33, and most TLRs. (springer.com)
- In this issue of the JCI, Das and colleagues report an association between early therapy-induced changes in circulating B cells and an increased risk of high-grade immune-related adverse events (IRAEs) in patients treated with checkpoint inhibitors that target cytotoxic T lymphocyte-associated antigen-4 (CTLA4) and programmed cell death protein 1 (PD1). (jci.org)
- They are abnormally expressed, but the immune system does see them as a normal cell protein," and the result is "more of a wound-healing type of response. (ascopost.com)
- Nivolumab is an immune checkpoint inhibitor targeting programmed death-1 protein and has been approved for the treatment of multiple advanced malignancies. (biomedcentral.com)
- In 2011, the Food and Drug Administration (FDA) approved Yervoy (ipilimumab), the first checkpoint inhibitor to target cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), which is a protein receptor that holds back immune response. (egfrcancer.org)
- Programmed cell death protein 1 (PD-1) also plays a role. (egfrcancer.org)
- A protein called programmed death-ligand 1 (PD-L1) connects to the PD-1 receptor and puts the brakes on the immune system. (egfrcancer.org)
- The binding of programmed death ligand 1 (PD-L1) to its receptor, programmed cell death protein 1 (PD-1) transmits signals that inhibit T- cell activation. (elsevier.com)
- Laminin expression by glial fibrillary acidic protein positive cells in human gliomas. (prp61.ru)
- CD274 (which codes for PD-L1) displays a very wide pattern of tissue gene expression, but PD-L1 is only seen at the protein level in myeloid cells, airway and kidney tubular epithelium, heart, placenta, and intestinal colon epithelium of inflammatory bowel disease (IBD) patients (6). (docme.ru)
- Both in innate immunity and in acquired immunity, some co-suppressor molecules on the surface of immune cells play important roles in immunosuppression, such as, programmed death receptor-1 (PD-1), T cell immunoglobulin and mucin-containing protein-3 (TIM-3), cytotoxic T lymphocyte associated antigen-4 (CTLA-4), natural killer cell receptor 2B4 (CD244), B and T lymphocyte attenuator (BTLA) and NKG2A (CD94), et al. (bvsalud.org)
- In the present study, we examined the in vivo activity of a humanized anti-programmed cell death protein 1 (anti-PD-1) antibody against triple-negative breast cancer (TNBC) patient-derived xenograft (PDX) tumor models. (biomedcentral.com)
- We have investigated the role of PD-1, an inhibitory TNFR family protein expressed on CTLs, in limiting the efficacy of immune-mediated control of metastatic osteosarcoma. (elsevier.com)
- Increased Innate Lymphoid Cells in Periodontal Tissue of the Murine Model of Periodontitis: The Role of AMP-Activated Protein Kinase and Relevance for the Human Condition Front Immunol. (usc.edu)
- Isoaspartylation appears to trigger small cell lung cancer-associated autoimmunity against neuronal protein ELAVL4 J Neuroimmunol. (usc.edu)
- Symptomatic disease was associated with increased glomerular Nod-like receptor protein 3 (NLRP3) and increased positivity for autophagy marker Microtubule-associated protein light chain 3 (LC3). (iastate.edu)
- In line with this hypothesis, CAR-T cell cytotoxicity was strongly inhibited in non-infected fibroblasts by expression of the HCMV-protein UL37x1, and even more so by additional expression of UL36. (pubmedcentralcanada.ca)
- it relies on host immunity mobilization to produce antiviral components, such as interleukin-12 and IFN-γ, and to induce the differentiation of adaptive immunocytes, which block viral protein synthesis and assemblage of viral structures. (biomedcentral.com)
- Ipilimumab targets the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) receptor. (biomedcentral.com)
- Nivolumab and pembrolizumab target programmed cell death protein 1 (PD-1) receptors and have proven to be superior to ipilimumab alone. (biomedcentral.com)
- The engagement of PD-L1 (and PD-L2) with the programmed cell death protein 1 (PD-1) receptor on CTL leads to T cell exhaustion. (biomedcentral.com)
- Another mechanism of dampened immune response that is thought to predominately exert its effects in secondary lymphoid organs, as opposed to within the TME, involves cytotoxic T lymphocyte-associated protein 4 (CTLA-4) expression on T cells. (biomedcentral.com)
Innate and adaptive immunity3
- Vasoactive intestinal peptide (VIP) is a multifunctional endogenous polypeptide that modulates both innate and adaptive immunity at multiple levels of immune cell differentiation and activation ( 1 ). (jimmunol.org)
- Innate and adaptive immunity play important protective roles by combating herpes simplex virus 1 (HSV-1) infection. (asm.org)
- Several mechanisms have been reported to participate in sepsis-induced immune alterations affecting both innate and adaptive immunity. (biomedcentral.com)
- MiR-34a is an important p53 downstream tumor suppressor, which regulates apoptosis, cell-cycle, EMT (epithelial mesenchymal transition), and so forth. (hindawi.com)
- The powerful tumor suppressor p53 is a transcription factor, which plays a crucial role in the regulation of cell-cycle, apoptosis, DNA repair, senescence, and angiogenesis [ 5 ]. (hindawi.com)
- On the other hand, many herbal extracts have been shown to induce growth arrest or apoptosis of cancer cells via p53 activation [ 8 - 13 ]. (hindawi.com)
- During the course of acute infection with an intracellular pathogen, Ag-specific T cells proliferate in the expansion phase, and then most of the T cells die by apoptosis in the following contraction phase, but the few that survive become memory cells and persist for a long period of time. (jimmunol.org)
- These results suggest that IL-15 plays a critical role in protecting effector CD8 + T cells from apoptosis during the contraction phase following a microbial infection via inducing antiapoptotic molecules. (jimmunol.org)
- Most of the activated T cells die by apoptosis during the contraction phase, but the few that survive become memory cells and persist for a long period of time ( 1 , 2 , 3 ). (jimmunol.org)
- The size of memory CD8 + T cell pool is dependent on the amounts of surviving T cells from T cell contraction by apoptosis after primary TCR-mediated activation. (jimmunol.org)
- At least two types of cell death can occur in activated T cells during the contraction phase: activation-induced cell death ( 3 ), also called Ag-driven apoptosis, and activated T cell autonomous cell death (ACAD) 3 , also called growth factor withdrawal-induced apoptosis ( 4 , 5 , 6 ). (jimmunol.org)
- The receptor programmed death-1 (PD-1) is also expressed on T cells following activation, where, on binding to its ligands PD-L1 and PD-L2, it promotes T-cell anergy, apoptosis, and exhaustion. (pnas.org)
- and (2) subsequently contacting the cell surface with a composition comprising a second member of the binding pair selected from the group consisting of avidin or streptavidin linked to a death ligand selected from the group consisting of Fas ligand (FasL), and the extracellular portion of Fas ligand to form a decorated cell surface, wherein the decorated cell surface is capable of inducing apoptosis. (google.com)
- A useful alteration of cell function is the induction of apoptosis. (google.com)
- First, it promotes apoptosis (programmed cell death) of antigen-specific T-cells in lymph nodes. (wikipedia.org)
- Second, it reduces apoptosis in regulatory T cells (anti-inflammatory, suppressive T cells). (wikipedia.org)
- In a screen for genes involved in apoptosis, Yasumasa Ishida, Tasuku Honjo and colleagues at Kyoto University in 1992 discovered and named PD-1. (wikipedia.org)
- The aim of this study was to assess the involvement of oxidative stress-induced apoptosis in cells from 16 Italian CADASIL patients. (antibiotika365.com)
- In vitro PD-1 blocking rescued M. tuberculosis-specific interferon γ (IFN-γ)-producing T cells from undergoing apoptosis. (umn.edu)
- The interaction between the T-cell receptor complex (TCR) and antigenic peptides bound in surface MHC molecules provides the specificity that defines adaptive T-cell immunity. (pnas.org)
- Adaptive antiviral cellular immunity was increased in mCMV-infected VIP-KO mice compared with WT mice, with more Th1/Tc1-polarized T cells, fewer IL-10 + T cells, and more mCMV-M45 epitope peptide MHC class I tetramer + CD8 + T cells (tetramer + CD8 T cells). (jimmunol.org)
- Because the absence of VIP in immune cells increased innate and adaptive antiviral immunity by altering costimulatory and coinhibitory pathways, selective targeting of VIP signaling represents an attractive therapeutic target to enhance antiviral immunity. (jimmunol.org)
- Mice were ocularly infected with HSV-1 to evaluate the effects of restricted innate or adaptive TGF-β signaling during acute and latent infections. (asm.org)
- Here, we show that murine and human melanomas contain PD-1-expressing cancer subpopulations and demonstrate that melanoma cell-intrinsic PD-1 promotes tumorigenesis, even in mice lacking adaptive immunity. (edu.au)
- Immune checkpoint inhibitors, adaptive T-cell therapies, and vaccines can enlist and rev up the immune system and be combined with chemotherapy for added clinical benefit. (ascopost.com)
- Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. (nih.gov)
- The programmed death-1 (PD-1) and its ligand PD-L1 (B7-H1) signaling pathway has been the focus of much enthusiasm in the fields of tumor immunology and oncology with recent FDA approval of the anti-PD-1 antibodies pembrolizumab and nivolumab and the anti-PD-L1 antibodies durvalumab, atezolimuab, and avelumab. (frontiersin.org)
- The systematic comparison of anti-PD-L1 antibody glycosylation variants with different Fc-mediated potencies demonstrates that our glyco-optimization approach has the potential to enhance CD8 T cell-mediated anti-tumor activity which may improve the therapeutic benefit of anti-PD-L1 antibodies. (frontiersin.org)
- Two anti-PD-1 antibodies were approved for different indications in the last 4 years: nivolumab (Bristol-Myers Squibb) and pembrolizumab (Merck & Co.). Similarly, the following anti-PD-L1 antibodies have recently been approved for specific indications: atezolizumab (MPDL3280A, Genentech), avelumab (EMD Serono and Pfizer), and durvalumab (AstraZeneca). (frontiersin.org)
- Disabling the function of immune checkpoint molecules can unlock T-cell immunity against cancer, yet despite remarkable clinical success with monoclonal antibodies (mAb) that block PD-1 or CTLA-4, resistance remains common and essentially unexplained. (aacrjournals.org)
- Antibodies that bind to either PD-1 or PD-L1 and therefore block the interaction may allow the T-cells to attack the tumor. (wikipedia.org)
- These are most likely due to the breadth of the induced T-cell activation when anti-CTLA-4 antibodies are administered by injection in the blood stream. (wikipedia.org)
- In mouse models of melanoma, tumor growth can be transiently arrested via treatment with antibodies which block the interaction between PD-L1 and PD-1. (bxcell.com)
- Summary Therapeutic antibodies targeting programmed cell death 1 (PD-1) activate tumor-specific immunity and have shown remarkable efficacy in the treatment of melanoma. (edu.au)
- PD-1 inhibition on melanoma cells by RNAi, blocking antibodies, or mutagenesis of melanoma-PD-1 signaling motifs suppresses tumor growth in immunocompetent, immunocompromised, and PD-1-deficient tumor graft recipient mice. (edu.au)
- In a previous study, a higher frequency of circulating PD-1 + CXCR5 + CD4 + Tfh cells was observed in patients with chronic schistosomiasis relative to healthy controls (HCs) and it correlated positively with the level of soluble egg antigen (SEA) specific antibodies in serum. (biomedcentral.com)
- Our previous study showed that Tfh cells might play an important role in the production of specific antibodies in chronic schistosomiasis patients [ 7 ], but their function in acute schistosomiasis patients is unknown. (biomedcentral.com)
- The clinical successes of ICIs, monoclonal antibodies (mAb) against CTLA-4 and PD-1 pathways, was a breakthrough achievement. (biomedcentral.com)
- First-generation immune checkpoint inhibitors, including anti-CTLA-4 and anti-programmed death 1 (anti-PD-1) antibodies, have led to major clinical progress, yet resistance frequently leads to. (jci.org)
- In this approach, monoclonal antibodies directly target specific receptors on myeloma cells. (cancernetwork.com)
- 3] Monoclonal antibodies not only target the myeloma cell itself, but they can also coordinate the immune response via upregulation of antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. (cancernetwork.com)
- New monoclonal antibodies targeting the programmed death 1/programmed death ligand 1 axis have also been studied in myeloma, and while ineffective as single agents, in combination with immunomodulatory drugs (lenalidomide and pomalidomide) they have demonstrated significant activity, validating this target in myeloma. (cancernetwork.com)
- Antibodies to CTLA-4 have been shown to block the interaction between CTLA-4 and its ligands, restoring the function of T cells in the antigen-presenting compartment [ 13 ]. (biomedcentral.com)
- 8) PD-1 has 2 major ligands: PD-L1/CD274 (encoded by PDCD1LG1 in chromosome 9) and PD-L2/CD273 (encoded by PDCD1LG2 in chromosome 9). (thefreelibrary.com)
- also called B7-H1 or CD274), which is expressed on many cancer and immune cells, plays an important part in blocking the 'cancer immunity cycle' by binding programmed death-1 (PD-1) and B7.1 (CD80), both of which are negative regulators of T-lymphocyte activation. (nih.gov)
- Its ligand, PD-L1 (B7-H1/CD274), is expressed on antigen-presenting cells. (aacrjournals.org)
- 0.001) but an inverse correlation with the expression of CD4 , CD8A , and T-cell effector function-related genes in the CD274 high rather than CD274 low group. (biomedcentral.com)
- The 10F.9G2 monoclonal antibody reacts with mouse PD-L1 (programmed death ligand 1) also known as B7-H1 or CD274. (bxcell.com)
- Objective Evidence suggests that CD274 (programmed death-ligand 1, B7-H1) immune checkpoint ligand repress antitumour immunity through its interaction with the PDCD1 (programmed cell death 1, PD-1) receptor of T lymphocytes in various tumours. (elsevier.com)
- We hypothesised that tumour CD274 expression levels might be inversely associated with T-cell densities in colorectal carcinoma tissue. (elsevier.com)
- We conducted multivariable ordinal logistic regression analyses to examine the association of tumour CD274 expression with CD3 +, CD8 +, CD45RO (PTPRC) + or FOXP3 + cell density in tumour tissue, controlling for potential confounders including tumour status of microsatellite instability (MSI), CpG island methylator phenotype, long interspersed nucleotide element-1 methylation level and KRAS, BRAF and PIK3CA mutations. (elsevier.com)
- Results CD274 expression in tumour cells or stromal cells (including immune cells) was detected in 731 (89%) or 44 (5%) cases, respectively. (elsevier.com)
- Tumour CD274 expression level correlated inversely with FOXP3 + cell density in colorectal cancer tissue (outcome) (p trend =0.0002). (elsevier.com)
- CD274 expression was not significantly associated with CD3 +, CD8 + or CD45RO + cell density, pathological lymphocytic reactions or patient survival prognosis. (elsevier.com)
- This system is composed of PD-1 (CD279) and its two ligands, PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC, CD273). (biomedcentral.com)
- In this second article in the present series, current understanding regarding the involvement of T-cells and antigen-presenting cells is summarised, with emphasis on the interaction between these two types of immune regulatory cells by means of co-stimulatory molecules. (ersjournals.com)
- The signaling events that are initiated downstream of CD80 are still under investigation, but have been shown to have similar effects on CD8 + T cell function as signaling downstream of the PD-L1/PD-1 interaction ( 9 - 11 ). (frontiersin.org)
- No differences were observed regarding binding to PD-L1 and blocking of this interaction with its counter receptors PD-1 or CD80. (frontiersin.org)
- Our study highlights an interaction among CD8 + T cells infiltration, PD-L1 expression, and CD44 + /CD133 + CSCs existence, which contributes to PC progression and immune evasion. (mdpi.com)
- Recently, an additional coinhibitory ligand/receptor interaction has been described that involves binding of PD-L1 on T cells to B7-1 on APCs or vice versa ( 3 ). (pnas.org)
- Upon interaction with their respective counterparts, various intracellular signalling pathways can be modified leading to altered effector functions  . (prolekare.cz)
- however, the interaction between these cell death pathways in vivo is unclear. (bvsalud.org)
- Most research into the PD-1/PD-L1 pathway has focused on the PD-1/PD-L1 interaction between target cells and immune cells. (biomedcentral.com)
- Exon 2 encodes the short linker ID, while the last three exons encode the C-terminal TIR domain, which mediates the interaction of MyD88 with other TIR domain receptors. (springer.com)
- The 10F.9G2 antibody has been shown to block the interaction between PD-L1 and PD-1 and between PD-L1 and B7-1 (CD80). (bxcell.com)
- On interaction of PD-1 with its ligands PD-L1 (B7-H1) or PD-L2 (B7-DC), the tyrosine-phosphorylated ITSM of PD-1 recruits a src homology 2 domain-containing tyrosine phosphatase 2, which mediates the dephosphorylation signaling and reduces lymphocyte activation ( 3 ). (diabetesjournals.org)
- Blocking the interaction between these co-suppressor molecules and their ligands can significantly reverse the immunosuppressive state in septic animal models or patients. (bvsalud.org)
- Harada K, Isse K, Nakanuma Y (2006) Interferon gamma accelerates NF-kappaB activation of biliary epithelial cells induced by Toll-like receptor and ligand interaction. (springermedizin.de)
- In the TME, immune suppression is mainly mediated by immunosuppressive cells, including regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and M2 macrophages. (biomedcentral.com)
- At baseline, all the tumor models studied were predominantly infiltrated with cells harboring an immunosuppressive phenotype. (bxcell.com)
- Programmed death ligand 1 (PD-L1) is expressed on antigen-presenting cells and inhibits activation of T cells through its receptor PD-1. (aacrjournals.org)
- Interference with PD‐L1/PD‐1 signalling markedly inhibits TCR down‐modulation leading to hyper‐activated, proliferative CD8 T cells as assessed in vitro and in vivo in an arthritis model. (embopress.org)
- Upon ligand binding, inhibits T-cell effector functions in an antigen-specific manner. (axolbio.com)
- Vitamin D inhibits inflammatory T cells via PD-L1 JBC Papers in Press. (docme.ru)
- Recently, it has become well known that immune checkpoint pathways, including the programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) signaling pathway, (2) which are important in mediating self-tolerance and controlling self-damage, can sometimes be manipulated by cancer cells to evade immune surveillance (as illustrated in Figure 1). (thefreelibrary.com)
- In this review, we will discuss the mechanism of the PD1/PD-L1 signaling pathway, the regulation of this pathway, PD-1/PD-L1 as a predictive and/or prognostic marker in various cancers, and strategies for measuring PD-L1 expression. (thefreelibrary.com)
- The PD-1/PD-L1 pathway belongs to the immune checkpoint signaling pathways regulating T-cell-mediated local inflammatory reactions and self-tolerance. (thefreelibrary.com)
- The programmed death-1 (PD-1) pathway is important in the maintenance of peripheral tolerance and homeostasis through suppression of T cell receptor signaling. (springer.com)
- Dysregulation of the PD-1/PD-L1 pathway has been implicated in a wide variety of diseases. (aacrjournals.org)
- Both the programmed death (PD) 1-PD-ligand (PD-L) pathway and regulatory T (T reg) cells are instrumental to the maintenance of peripheral tolerance. (rupress.org)
- Methods HRS cells from archival tumor biopsies were evaluated for 9p24.1 alterations by fluorescence in situ hybridization and for expression of PD ligand 1 (PD-L1) and the antigen presentation pathway components-β2-microglobulin, MHC class I, and MHC class II-by immunohistochemistry. (elsevier.com)
- The programmed cell death-1 (PD-1)/ programmed cell death-ligand (PD-L) pathway acts as an immune checkpoint for tumor cells to evade host immune surveillance [ 1 , 2 ]. (biomedcentral.com)
- Yet, little is known about tumor cell-intrinsic PD-1 pathway effects. (edu.au)
- Viruses and tumour cells take advantage of this pathway to escape the host's immune defences. (biomedcentral.com)
- Targeting of the sialoglycan-SAMP/Siglec pathway in vitro and in vivo resulted in increased anticancer immunity. (jci.org)
- Therefore, it is conceivable that activated human T cells may be regulated directly by the SE-calreticulin pathway. (scirp.org)
- It is important to note that PD-L1 also interacts with CD80 (B7-1), which is expressed on the surface of CD8 + T cells. (frontiersin.org)
- In addition to its function as a ligand for PD-1, PD-L1 can additionally bind to CD80 also resulting in inhibition of T cell activation ( 7 ). (frontiersin.org)
- Following mCMV infection there was a marked upregulation of MHC-II and CD80 costimulatory molecule expression on DC from VIP-KO mice compared with DC from WT mice, whereas programmed death-1 and programmed death ligand-1 expression were upregulated in activated CD8 + T cells and DC, respectively, in WT mice, but not in VIP-KO mice. (jimmunol.org)
- In murine systems, melanoma cells engineered to express PD-L1 are resistant to cytotoxic T lymphocyte (CTL)-mediated lysis and exhibit more aggressive tumor growth than wild-type melanoma ( 21 ). (aacrjournals.org)
- This may explain why carcinogen-induced cancer, like lung squamous cell carcinoma and melanoma, is often accompanied by inflammation, as the DNA damage response is a major trigger activating the innate immune response. (iiarjournals.org)
- PD-L1 is expressed on almost all murine tumor cell lines, including PA1 myeloma, P815 mastocytoma, and B16 melanoma upon treatment with IFN-γ. (wikipedia.org)
- 100 genes-including Pbrm1 , Arid2 , and Brd7 , which encode components of the PBAF form of the SWI/SNF chromatin remodeling complex-sensitized mouse B16F10 melanoma cells to killing by T cells. (sciencemag.org)
- Melanoma Cell-Intrinsic PD-1 Receptor Functions Promote Tumor Growth" by S. Kleffel, C. Posch et al. (edu.au)
- 2015). Melanoma Cell-Intrinsic PD-1 Receptor Functions Promote Tumor Growth in Cell, 162(6), 1242-1256. (edu.au)
- Conversely, melanoma-specific PD-1 overexpression enhances tumorigenicity, as does engagement of melanoma-PD-1 by its ligand, PD-L1, whereas melanoma-PD-L1 inhibition or knockout of host-PD-L1 attenuate growth of PD-1-positive melanomas. (edu.au)
- Mechanistically, the melanoma-PD-1 receptor modulates downstream effectors of mTOR signaling. (edu.au)
- Our results identify melanoma cell-intrinsic functions of the PD-1:PD-L1 axis in tumor growth and suggest that blocking melanoma-PD-1 might contribute to the striking clinical efficacy of anti-PD-1 therapy. (edu.au)
- After both PDXs and melanoma cell xenografts reached ~ 150-200 mm 3 , animals were treated with humanized anti-PD-1 antibody or anti-CTLA-4 and evaluated for tumor growth, survival, and potential mechanism of action. (biomedcentral.com)
- Advanced melanoma has historically been associated with a poor prognosis, with a median overall survival (OS) of 8-10 months and a 5-year survival rate of 10 % [ 1 ]. (biomedcentral.com)
- Expression of CRK28 in Nicotiana benthamiana induced cell death, which required intact extracellular Cys residues and a conserved kinase active site. (plantphysiol.org)
- PTI receptors are receptor-like kinases (RLKs) or receptor-like proteins (RLPs) possessing extracellular ligand-binding domains ( Zipfel, 2014 ). (plantphysiol.org)
- 3. The method of claim 1 , wherein said death ligand is the extracellular portion of Fas ligand. (google.com)
- 4. The method of claim 3 , wherein said composition comprises a chimeric composition of streptavidin linked to the extracellular portion of Fas ligand and wherein said chimeric composition is encoded by a nucleic acid having the sequence of SEQ ID NO:1. (google.com)
- Transfecting PD-L1 in PD-L1 low cells enhanced hexokinase-2 (HK2) expression, lactate production, and extracellular acidification rates, but minimally altered GLUT1 and PKM2 expression and oxygen consumption rates. (biomedcentral.com)
- In this study, we identify a novel and structurally distinct Ig superfamily inhibitory ligand, whose extracellular domain bears homology to the B7 family ligand PD-L1. (rupress.org)
- Emerging evidence suggests key roles of tumor extracellular matrix (ECM) components and their proteolytic remodeling products in regulating each step of the cancer-immunity cycle. (biomedcentral.com)
- Here we show that the inhibitory T cell costimulatory molecule, programmed death ligand 1 (PDL1), has an important role in conferring fetomaternal tolerance in an allogeneic pregnancy model. (rupress.org)
- CTLA-4 is a key molecule expressed on the surface of T cells. (prolekare.cz)
- We suggest that 2B4 is another important molecule within the network of costimulatory/inhibitory receptors regulating CD8+ T cell function in acute and chronic hepatitis C and that 2B4 expression levels could also be a marker of CD8+ T cell dysfunction. (prolekare.cz)
- In mouse models of persistent viral infections exhaustion of virus-specific CD8+ T cells was shown to be linked to the expression of the coinhibitory molecule PD1  ,  . (prolekare.cz)
- Programmed cell death ligand 1 (PD-L1) is an immunomodulatory molecule expressed by antigen-presenting cells as well as by certain tumour cells. (cancerworld.net)
- This molecule is designated V-domain Ig suppressor of T cell activation (VISTA). (rupress.org)
- 12 . The method of claim 11 wherein the molecule is selected from Fas ligand and CD27. (google.com)
- Herein, perspectives regarding co-inhibitory receptors' contribution to lymphocyte exhaustion in sepsis will be discussed in the context of a recently published study investigating the potential of PD-1 molecule expression (i.e. (biomedcentral.com)
- 1 ] provides further insights regarding the potential of Programmed Death-1 (PD-1)-related molecule expression to predict mortality in septic shock patients. (biomedcentral.com)
- Indeed, the best result for predicting mortality is not obtained with PD-1-related molecule expressions on lymphocytes but rather with PD-L1 expression on monocytes. (biomedcentral.com)
- In general, high densities of myeloid cells, that is, macrophages and myeloid-derived suppressor cells (MDSC), correlate with poor prognosis ( 6 ). (aacrjournals.org)
- Here, we found that macrophages from patients with CAD actively suppress T cell activation and expansion, leading to defective VZV-specific T cell immunity. (stanford.edu)
- Monocyte-derived and plaque-infiltrating macrophages from patients with CAD spontaneously expressed high surface density of the immunoinhibitory ligand programmed death ligand-1 (PD-L1), thereby providing negative signals to programmed death-1+ (PD-1+) T cells. (stanford.edu)
- PD-L1 is constitutively expressed on mouse APCs (DCs, macrophages, and B cells) and T cells and is further up-regulated upon activation. (rupress.org)
- Myeloid cells, including macrophages and immature myeloid cells/myeloid-derived suppressor cells (MDSCs), accumulate during the progression of pancreatic cancer. (bmj.com)
- Furthermore, enforced expression of Bcl-2 protected the majority of effector OT-I cells from death in IL-15 KO mice after infection. (jimmunol.org)
- Therefore, identification of molecular mechanisms responsible for activated T cell death during the contraction phase is important for our understanding how memory develops after infection with microbes. (jimmunol.org)
- Conversely, upregulation of PD-1 signaling is associated with the persistence of chronic infections, including HIV ( 5, 6 ), Helicobacter pylori infection ( 7 ), and schistosomiasis ( 8 ). (aacrjournals.org)
- This consequence has been closely examined in the immune elimination process during viral infection and recently in the cancer immunity cycle ( 4 ). (iiarjournals.org)
- The aim of this study was to analyze the role of 2B4 as an additional costimulatory receptor regulating CD8+ T cell function and in particular to investigate its implication for exhaustion of hepatitis C virus (HCV)-specific CD8+ T cells during persistent infection. (prolekare.cz)
- Furthermore, inhibiting TGF-β signaling in T cells reduced cell lysis and leukocyte infiltration in corneas and trigeminal ganglia during primary HSV-1 infection of mice. (asm.org)
- Impaired basophil induction leads to an age-dependent innate defect in type 2 immunity during helminth infection in mice. (tcd.ie)
- Programmed death-1 levels correlate with increased mortality, nosocomial infection and immune dysfunctions in septic shock patients. (fichier-pdf.fr)
- The role of T follicular helper (Tfh) cells in schistosome infection is not fully defined. (biomedcentral.com)
- Given the relative severity of HIV-1 infection, the majority of studies have been done using HIV-1. (biomedcentral.com)
- The infection dynamics of HIV-1 are very interesting. (biomedcentral.com)
- Upon initial HIV-1 infection, there is a period of continuous viral replication and strong immune pressure against the virus, resulting in a relatively low steady state of viral load. (biomedcentral.com)
- Here, Bongers and colleagues show that US28, a constitutively active chemokine receptor encoded by CMV, can cause the development of intestinal dysplasia and cancer in transgenic mice and suggest that CMV infection may facilitate intestinal neoplasia in humans (page 3969). (jci.org)
- Roles of Type 1, 2, and 3 Innate Lymphoid Cells in Herpes Simplex Virus 1 Infection In Vitro and In Vivo J Virol. (usc.edu)
- Efficacy of Rhesus Theta-Defensin-1 in Experimental Models of Pseudomonas aeruginosa Lung Infection and Inflammation Antimicrob Agents Chemother. (usc.edu)
- Impairment of cell lysis became detectable 1 day after HCMV infection and gradually increased during the following 3 days. (pubmedcentralcanada.ca)
- Human cytomegalovirus infection after hematopoietic stem cell transplantation is associated with substantial morbidity and mortality. (pubmedcentralcanada.ca)
- However, during the progression of chronic HBV infection, T cell dysfunction is too profound to effectively control viral replication, leading to a decline of viral clearance. (biomedcentral.com)
- The response to PD-1/PD-L1 inhibition has been mixed in various malignancies such as colorectal, prostatic and pancreatic adenocarcinomas and is exemplified in the results of a study by Brahmer et al. (biomedcentral.com)
- Although the existence of so many layers of T-cell inhibition may seem surprising, the severe and sometimes fatal autoimmunity that results when even one of these pathways is disrupted attests to their necessity. (pnas.org)
- Experiments using PD-L1 transfected DCs and PD-1 expressing transgenic (Tg) CD4+ and CD8+ T cells suggest that CD8+ T cells are more susceptible to inhibition by PD-L1, although this could be dependent on the strength of TCR signaling. (wikipedia.org)
- PD-1 has two cytoplasmic tyrosine motifs: one an immunoreceptor tyrosine-based inhibition motif and the other an immunoreceptor tyrosine-based switch motif (ITSM). (diabetesjournals.org)
- Can you link to those articles you mention as showing relationship between TCR status and PD-1 inhibition prognosis? (b-t.cr)
- On the other hand if tumor cells are expressing PD-L1 they are likely to respond to PD-1 inhibition and if they don't express PD-L1 at all, well then there is a clear cut case where PD-1 inhibition is useless. (b-t.cr)
- So then succesful PD-1 inhibition would be reflected in a temporarily lower diversity TCR repertoire. (b-t.cr)
- All the titles seems to imply that the articles are about the PD-1 inhibition and its potential to enable T cell response against tumor specific antigens. (b-t.cr)
- Despite strong degranulation and cytokine production by the T cells, we again found significant inhibition of lysis of HCMV-infected cells. (pubmedcentralcanada.ca)
- T cell inhibition via this receptor occurs through multiple mechanisms. (biomedcentral.com)
- 3,4) The fact that PD-1 is highly upregulated in tumor-infiltrating lymphocytes, as well as the correlation between PD-L1 expression and clinical outcome of patients in many types of solid cancers, has resulted in some seminal clinical trials. (thefreelibrary.com)
- Tumor-infiltrating T lymphocytes (TILs) express high levels of PD-1 ( 8 ). (frontiersin.org)
- In the tumor milieu, activated cytotoxic T lymphocytes (CTLs) are rapidly suppressed by these cells and become anergic, a state of reversible unresponsiveness, or die. (nih.gov)
- Naturally occurring anti-tumor T lymphocytes previously controlled by immune evasion strategies are then released from restraint and can recognize and kill tumor cells. (nih.gov)
- Any immunity in breast cancer where lymphocytes are concerned is good immunity, which means that it can potentially be harnessed. (ascopost.com)
- PD-1 on lymphocytes, PD-L1 on monocytes) to predict mortality in septic shock patients. (biomedcentral.com)
- The first report on the specific cytokine profile of T-cells involved in the pathogenesis of human asthma was published in the early 1990s, demonstrating that T-cells in bronchoalveolar lavage fluid (BALF) from asthmatic patients predominantly produce the Th2-type cytokines granulocyte-macrophage colony-stimulating factor and IL-3, -4 and -5 5 , 6 . (ersjournals.com)
- Similarly, athymic mice with no functional peripheral T-cells also lack eosinophilic airway infiltration and increased AHR following allergen sensitisation, unless production of the Th2 cytokine IL-5 is restored by systemic administration 9 . (ersjournals.com)
- Conversely, acute segmental allergen challenges lead to a reduction in Th1 cytokine-producing T-cell numbers 16 . (ersjournals.com)
- The mechanisms leading to exhaustion of T cells are only partially understood, beside changes in the cytokine milieu and the lack of CD4+ T cell help  ,  , altered expression levels of coinhibitory molecules may also be of importance. (prolekare.cz)
- IFN-γ is a key pro-inflammatory cytokine that promotes T cell inflammatory activity. (wikipedia.org)
- This is consistent with the observations that cytokine production, cytotoxic activity, and clonal expansion were significantly enhanced in T-cells and antigen-presenting cells from PD-L1 −/− mice, compared with cells from wild-type or PD-L2 −/− mice ( 9 , 10 ). (diabetesjournals.org)
- In co-culture experiments with primary human T cells, epithelial cells pre-treated with 1,25D suppressed activation of CD4+ and CD8+ cells and inhibited inflammatory cytokine production in a manner that was abrogated by anti-PD-L1 blocking antibody. (docme.ru)
- In vitro stimulation of peripheral blood mononuclear cells in the presence of Mycobacterium tuberculosis antigens was performed with and without blocking PD-1, and intracellular cytokine production was measured by FACS. (umn.edu)
- Herein, we demonstrate that the majority of CD4+ and CD8+ KITs in 3 murine lupus models are not effector cells, as hypothesized, but rather express multiple inhibitory receptors and are highly dysfunctional, with reduced cytokine production and proliferative capacity. (jci.org)
- Activation-induced cell death is triggered mostly through cell surface proteins of the TNFR family, including Fas (CD95) ( 7 , 8 , 9 ). (jimmunol.org)
- Although the involvement of Th2 cytokines explains the biological basis of many features of the allergic reaction ( e.g. recruitment of eosinophils, activation of mast cells, airway remodelling and IgE production), it has been observed more recently that asthmatic individuals may also exhibit an increased Th1-like response to allergens 10 , 11 , especially in established disease 12 - 15 . (ersjournals.com)
- Cells from the lymphoid, endothelial, and epithelial lineages, including cancer cells from these lineages, express PD-L1 upon activation by IFN-γ and TNF-α ( 4 ). (frontiersin.org)
- SHP-1 and SHP-2 dephosphorylate the immunoreceptor tyrosine-based activation motifs of the TCR, thus dampening the signaling downstream of the TCR ( 7 ). (frontiersin.org)
- Although CTLA-4 and PD-1 belong to the same family of molecules and are both coinhibitory, evidence suggests they use distinct nonredundant mechanisms to inhibit T-cell activation. (pnas.org)
- PD-1 is up-regulated on T cells upon activation, and its ligands have distinct expression patterns, with PD-L1 being expressed much more broadly than PD-L2. (rupress.org)
- Our study addresses a fundamental immunological mechanism for the control of T cell activation during antigen presentation, TCR down‐modulation. (embopress.org)
- This finding expands the role of PD‐L1 in immune regulation to a critical step in T cell activation. (embopress.org)
- hence, blocking its function, either alone or in combination with other therapies, leads to improved T-cell activation and expansion [ 5 - 7 ]. (prolekare.cz)
- T cell activation and differentiation induce VPAC2 expression, whereas VPAC1 is downregulated following stimulation of human blood T cells with anti-CD3 mAb plus PMA ( 10 ). (jimmunol.org)
- Depletion of MDSC or macrophage subsets results in increased infiltration and activation of CD8 + T cells. (bmj.com)
- The mechanism of action of ilixadencel is to induce recruitment and activation of endogenous immune cells, including NK cells that subsequently promotes cross-presentation of cell-associated tumor antigens by co-recruited DCs. (springer.com)
- Jurkat T-cell activation was assessed after co-culture with NSCLC cells. (biomedcentral.com)
- Interferon-γ (IFNγ) secretion and activation marker expression was decreased in stimulated Jurkat T-cells when co-cultured with HK2-overexpressing vector-transfected tumor cells rather than empty vector-transfected tumor cells. (biomedcentral.com)
- In this study, we explored the role of GPR55 in advanced glycation end productions (AGEs)- induced chondrocytes activation in cultured cells. (bvsalud.org)
- Myeloid differentiation primary response gene 88 (MyD88) was originally discovered and cloned by Liebermann and Hoffman in 1990 as one of the 12 different mRNA transcripts that were induced in M1 myeloblastic leukemia cells upon activation with lung-conditioned medium or recombinant interleukin (IL)-6 (Lord et al. (springer.com)
- In this issue of the JCI, Rossi and colleagues tested the hypothesis that activation of hepatic Gi-coupled receptors, which should inhibit cAMP production, would oppose the cAMP-inducing action of glucagon and thereby decrease HGP. (jci.org)
- These observations indicate that PD-1 is a critical negative regulator of lymphocyte activation and that the phenotype of PD-1 deficiency-induced autoimmunity is highly influenced by other genetic factors. (diabetesjournals.org)
- variable fragment with signaling endodomains associated with T-cell activation. (1library.net)
- While every Ebola-infected patient showed massive T-cell activation irrespective of outcome, the increased expression of these immune checkpoint molecules marked fatal evolution in some patients and correlated with high viraemia [ 10 ]. (biomedcentral.com)
- Activated PD-1 negatively regulates T-cell activation and and plays a key role in in tumor evasion from host immunity. (cancer.gov)
- There is recruitment of immune cells and activation of bone remodeling that can lead to deformed joints and disability. (scirp.org)
- It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. (nih.gov)
- Antibody-drug conjugates (ADCs) are intended to bind to specific positive target antigens and eradicate only tumor cells from an intracellular released payload through the lysosomal protease. (biomedcentral.com)
- They induce the synthesis of allergen-specific immunoglobulin (Ig)E and recruit and activate effector cells, such as eosinophils, via the secretion of soluble factors. (ersjournals.com)
- PD-L1-coated beads induce iT reg cells in vitro, indicating that PD-L1 itself regulates iT reg cell development. (rupress.org)
- In order to induce effective immunity against a tumor, increased immunogenicity of the tumor itself is necessary. (prolekare.cz)
- It has long been the goal of experimental biology and medicine to induce cells to behave in predictable ways and to alter the behavior of cells in ways that are beneficial to a subject. (google.com)
- under the 5 endothelial enhancer of the come cell leukaemia locus (End-SCL-Cre-ER(Capital t)) in order to induce endothelial-FAK-deletion in adult mice (Weis et al, 2008). (bostonscienceandengineeringlectures.com)
- Evidence suggests that inflammation caused by immune infiltration can induce immune escape mechanisms, including interferon (IFN)-gamma-mediated upregulation of programmed death-ligand 1 (PD-L1) in the TME and increased numbers of regulatory T cells (Tregs) [ 8 ]. (biomedcentral.com)
- Using an adoptive transfer system of OT-I cells expressing OVA 257-264 /K b -specific TCR into control, IL-15 knockout (KO) and IL-15 transgenic (Tg) mice followed by challenge with recombinant Listeria monocytogenes expressing OVA, we found that the survival of CD44 + CD62L − CD127 − effector OT-I cells during the contraction phase is critically dependent on IL-15. (jimmunol.org)
- In correlation with the expression level of Bcl-2 in OT-I cells, the number of OT-I cells was markedly reduced in IL-15 KO mice but remained at a high level in IL-15 Tg mice during the contraction phase, compared with control mice. (jimmunol.org)
- In vivo administration of rIL-15 during the contraction phase in IL-15 KO mice inhibited the contraction of effector OT-I cells accompanied by up-regulation of Bcl-2 expression. (jimmunol.org)
- However, recent studies using Fas/Fas ligand mutant or Fas/TNFRI-deficient mice have demonstrated that neither Fas/Fas ligand nor TNFRI is required for T cell death during the contraction phase ( 10 , 11 , 12 , 13 , 14 ). (jimmunol.org)
- Most strikingly, CTLA-4 knockout mice die by 4 weeks of age from a lethal lymphoproliferative disorder, whereas some colonies of PD-1 knockout BL6 mice live over a year before manifesting lupus-like symptoms with ∼50% penetrance ( 8 , 9 ). (pnas.org)
- mCMV-infected VIP-KO mice had lower viral loads, faster clearance of virus, with increased numbers of IFN-γ + NK and NKT cells, and enhanced cytolytic activity of NK cells. (jimmunol.org)
- mCMV-immune VIP-KO mice had enhanced ability to clear mCMV peptide-pulsed target cells in vivo. (jimmunol.org)
- Even though VIP and PACAP signal through the same receptors, PACAP does not fully compensate for the loss of VIP in VIP-knockout (VIP-KO) mice ( 8 ). (jimmunol.org)
- VIP-KO mice lack compensatory increase in PACAP peptide expression, and expression of the VPAC1 and VPAC2 VIP receptors is diminished in brains of VIP-KO mice ( 8 ). (jimmunol.org)
- In a mouse model of allogeneic BM transplantation, DC that were differentiated in the presence of VIP, and then transplanted along with BM cells and splenic T cells, induced the generation of regulatory T cells and protected mice from acute graft versus host disease ( 12 ). (jimmunol.org)
- Methods Primary mouse pancreatic cancer cells were transplanted into CD11b-diphtheria toxin receptor (DTR) mice. (bmj.com)
- These mice have specific TGF-β signaling blockades in either T cells or innate cells. (asm.org)
- Limiting innate cell but not T cell TGF-β signaling reduced virus replication in the eyes of infected mice. (asm.org)
- On the other hand, blocking TGF-β signaling in either innate cells or T cells resulted in decreased latency in the trigeminal ganglia of infected mice. (asm.org)
- To overcome developmental problems associated with the generation of TGF-β knockout mice and to specifically limit TGF-β signaling to immune cells, transgenic mice were generated using a dominant negative TGF-β RII (DNR) under innate cell (CD11c) or T cell (CD4) immune-specific promoters ( 27 , 36 ). (asm.org)
- Thus, in CD11cdnTGF-RII mice, the innate immune cells do not respond to TGF-β ligands, while T cells do not respond to TGF-β in CD4dnTGF-RII mice. (asm.org)
- Moreover, administration of systemic sFLT3L and local poly-ICLC enhanced DC-mediated cross-priming and synergized with anti-CD137- and anti-PD-1-mediated immunostimulation in tumor therapy against B16-ovalbumin-derived melanomas, whereas this function was lost in Batf3 −/− mice. (aacrjournals.org)
- PD-1 knockout mice have been shown to develop lupus-like glomerulonephritis and dilated cardiomyopathy on the C57BL/6 and BALB/c backgrounds, respectively. (wikipedia.org)
- Furthermore, anti-VISTA treatment exacerbates the development of the T cell-mediated autoimmune disease experimental autoimmune encephalomyelitis in mice. (rupress.org)
- We investigated the protective potential of PD-L1 on autoimmune diabetes by transgenically overexpressing PD-L1 in pancreatic β-cells in nonobese diabetic (NOD) mice. (diabetesjournals.org)
- CONCLUSIONS -Our results demonstrate the protective potential of transgenic PD-L1 in autoimmune diabetes and illustrate its role in downregulating diabetogenic T-cells in NOD mice. (diabetesjournals.org)
- PD-1 −/− mice on different genetic backgrounds develop distinct autoimmune phenotypes, such as lupus-like glomerulonephritis/arthritis in C57Bl/6 (B6) mice or anticardiac troponin I-mediated dilated cardiomyopathy in Balb/c mice ( 4 , 5 ). (diabetesjournals.org)
- Prevention of lymphocyte cell death in sepsis improves survival in mice. (fichier-pdf.fr)
- Consistent with previous observations of speciesspecific regulation of immunity by vitamin D, the VDREs are present in primate genes but neither the VDREs nor the regulation by 1,25D is present in mice. (docme.ru)
- PD-L1 is also expressed on the K7M2 osteosarcoma tumor cell line that establishes metastases in mice, and PD-1 is expressed on tumor-infiltrating CTLs during disease progression. (elsevier.com)
- Immunostaining of tumour blood ships from ECFAKWT and ECFAKKO mice indicated that the appearance level of Flk-1 was not modified suggesting that the legislation of angiogenesis by FAK is definitely downstream of Flk-1 (Supplementary Info Fig H11). (bostonscienceandengineeringlectures.com)
- In sepsis, pioneering work by Pr Ayala's group published in 2009 reported that PD-1 knockout mice exhibited greater capacity to clear bacteria and lower mortality after experimental sepsis [ 2 ]. (biomedcentral.com)
- While it is presently unknown if the SE directly affects TH17 cells in humans, our group has recently demonstrated that this sequence motif acts as a signal transduction ligand that facilitates TH17 polarization in mice [2, 12-14]. (scirp.org)
- While activated T cells in both humans and mice express membrane-associated calreticulin [19,20], only human T cells express MHC Class II molecules on their surface . (scirp.org)
- Impaired host immunity is thought to play a role in the pathogenesis and progression of lymphoma. (aacrjournals.org)
- PD-1 also may serve as a biomarker to monitor host immunity among patients with tuberculosis during therapy and vaccine studies. (umn.edu)
- it plays an important role in tumor evasion from host immunity. (cancer.gov)
- In most mouse models, anti-tumor immunity requires the generation of tumor-specific cytotoxic CD8 + T cells (CTLs) and it is similarly believed that CTLs are major players in successful immunotherapies of human cancers. (springer.com)
- In this case T cells recognising tumor specific epitopes are relieved from suppression and will therefore expand to take up a large part of the T cells and then dealing with the tumor. (b-t.cr)
- PD-1-PD-L interactions regulate peripheral CD4 and CD8 T cell tolerance at multiple checkpoints. (rupress.org)
- It is proposed to function downstream in the immune response, limiting the activity of T cells in peripheral tissues that express PD-L1, and thus reduce autoimmunity [ 10 - 12 ]. (prolekare.cz)
- VIP is secreted by neurons (in both the central and peripheral nervous systems) ( 2 ) and by B cells, T cells, accessory cells, and other nonlymphoid cells ( 3 - 6 ). (jimmunol.org)
- Oxygen consumption of human peripheral blood mononuclear cells in severe human sepsis. (fichier-pdf.fr)
- PD-1 + CXCR5 + CD4 + Tfh cells in peripheral blood are involved in the immune response of patients with acute schistosomiasis. (biomedcentral.com)
- Furthermore, the blockage of PD-1/B7.H1 improved superoxide production in canine monocyte-derived phagocytes, and resulted in improved parasite clearance from peripheral blood after 7 days of culture. (iastate.edu)
- Peripheral blood cells were isolated from 23 CHB patients who were treated with pegylated IFN-α at week 0 (baseline) and week 24. (biomedcentral.com)
- Peripheral blood mononuclear cells (PBMC) isolated at week 24 were re-challenged with exogenous HBV core antigen, and the percentage of IFN-γ expression, serum HBV DNA loads, and ALT (alanine aminotransferase) levels were evaluated. (biomedcentral.com)
- To explore potential mechanisms of RA susceptibility, we analyze in vitro effect of peptides bearing different HLA-DR4 sequences on human peripheral blood-derived cells. (scirp.org)
- The World Health Organization classification for peripheral T-cell lymphomas (PTCLs) continues to evolve based on genetic and clinical distinctions of each entity. (cancernetwork.com)
- Peripheral T-cell lymphomas (PTCLs) include a spectrum of mature T-cell and natural killer (NK)-cell neoplasms. (cancernetwork.com)
- 12 Graduate Programs in Immunology and Cancer Biology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA. (jci.org)
- Our study will be of interest to a broad range of basic researchers in cell biology, immunology, rheumatology as well as clinicians. (embopress.org)
- With the development of cancer molecular biology and immunology, targeted therapy for immune checkpoints of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has shown enormous development prospects for HNC treatment. (dovepress.com)
- Communication between T cells and APCs is bidirectional. (nih.gov)
- In other cases, activated T cells upregulate ligands, such as CD40L, that engage cognate receptors on APCs. (nih.gov)
- VISTA is primarily expressed on hematopoietic cells, and VISTA expression is highly regulated on myeloid antigen-presenting cells (APCs) and T cells. (rupress.org)
- PD-L2 expression is restricted to professional antigen presenting cells (APCs) and is generally present at much lower levels on the cell surface compared with PD-L1 (6). (docme.ru)
- Part 1 is a dose escalation phase to determine the maximally tolerated dose (MTD), and part 2, the expansion phase, is to better characterize the safety, tolerability, and anti-tumor activity of the drug at the MTD. (dana-farber.org)
- The programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis plays a central role in suppression of anti-tumor immunity. (frontiersin.org)
- These cells act together to promote tumor progression and suppress anti-tumor immune reactions. (nih.gov)
- PD-L1 enhances glycolysis in NSCLC by upregulating HK2, which might dampen anti-tumor immunity. (biomedcentral.com)
- PD-1 signaling has attracted intense interest for its role in a pathophysiological context: suppression of anti-tumor immunity. (docme.ru)
- In establishing cell lines from an aggressive PD-L1 + mature B-cell lymphoma, we also noted that PD-L1 expression could be lost under certain in vitro culture conditions. (aacrjournals.org)
- Through the VPAC1 receptor, VIP leads to the development of bone marrow (BM)-derived tolerogenic DCs in vitro and in vivo ( 11 ). (jimmunol.org)
- 2. The method of claim 1 , wherein (2) subsequently contacting the cell surface with a composition comprising a second member of the binding pair linked to a death ligand, occurs in vitro. (google.com)
- However, the crystal structure of the MyD88 DD in complex with DDs of IRAK4 (interleukin-1 receptor associated kinase 4)-IRAK2 (PDB ID: 3MOP) was solved in vitro in the absence of MyD88 TIR domain and of TLRs (Lin et al. (springer.com)
- Joplin R, Kachilele S (2009) Human intrahepatic biliary epithelial cell lineages: studies in vitro. (springermedizin.de)
- The responders had a higher IFN-γ expression in memory T cells than the non-responders did after HBV antigen re-stimulation in vitro . (biomedcentral.com)
- In male-derived T cells, all peptide treatments significantly reduced TH17 cell differentiation in vitro when compared to no peptide treatment, and to female samples. (scirp.org)
- In vitro studies have shown that SE ligand, either as linear peptides or as natively folded tetrameric HLADR proteins, were able to trigger production of reactive oxygen species (ROS) and nitric oxide (NO) . (scirp.org)
- we identified the presence of both CD4+ and CD8+ T cell exhaustion during symptomatic VL, mediated through coinhibitory receptor Programmed Death 1 (PD-1). (iastate.edu)
- Of these, the concept of 'cell exhaustion' has gained a lot of interest because some parallels can be drawn with the cancer field in which immunostimulation approaches through blocking immune checkpoints currently obtain remarkable success. (biomedcentral.com)
- Elevated expression of programmed death-1 and programmed death ligand-1 negatively regulates immune response against cervical cancer cells," Mediators of Inflammation , vol. 2016, Article ID 6891482, 11 pages, 2016. (hindawi.com)
- T cell receptor (TCR) down‐modulation after antigen presentation is a fundamental process that regulates TCR signal transduction. (embopress.org)
- The intracellular tail contains two phosphorylation sites located in an immunoreceptor tyrosine-based inhibitory motif and an immunoreceptor tyrosine-based switch motif, which suggests that PD-1 negatively regulates T-cell receptor TCR signals. (wikipedia.org)
- In addition, PD-1 ligation up-regulates E3-ubiquitin ligases CBL-b and c-CBL that trigger T cell receptor down-modulation. (wikipedia.org)
- The central hypothesis being tested in this proposal is that PD-L1 regulates cell cycle and chromosomal stability in triple negative breast cancer (TNBC), and targeting the intracellular/nuclear function of PD-L1 or pathways (mitosis and cohesin) regulated by PD-L1 is of therapeutic use. (elsevier.com)
- The aim of the study was to evaluate whether PD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (ICs) can be used as biomarker to predict recurrence-free survival (RFS), overall survival (OS) and disease-specific survival (DSS) in bladder cancer patients after radical cystectomy (RC) developing disease recurrence followed by first-line chemotherapy. (oncotarget.com)
- Hereby the quantification of overall PD-L1 expression on tumor cells or tumor-infiltrating immune cells ranged in primary tumor between 32% and 66% [ 2 - 3 ]. (oncotarget.com)
- Because PD‑L1 can be expressed by both the tumor cells themselves and also the host cells, including host immune cells, the actual mechanistic target of therapy has remained unclear. (jci.org)
- That is usually dictated by those innate immune cells, because when those antigen presenting cells get their signals, they start secreting cytokines," Dr. Disis said. (ascopost.com)
- In October 2018, the Nobel prize committee duly recognized two scientists, Dr. James Allison and Dr. Tasuku Honjo for their pioneering research in immune checkpoint therapy, an approach that involves harnessing one's own immune cells to attack tumor cells. (biomedcentral.com)
- The immune system is composed of immune as well as non-immune cells. (biomedcentral.com)
Squamous Cell Carc7
- Background/Aim: Lung squamous cell carcinoma often arises from precancerous lesions where alterations in tumor suppressor genes and subsequent chromosomal instability are often observed due to carcinogen exposure. (iiarjournals.org)
- Patients and Methods: An immunohistochemical analysis was performed in 41 consecutive lung squamous cell carcinoma patients who underwent surgery at our institution between April 2013 and March 2014. (iiarjournals.org)
- Conclusion: Our findings demonstrate that nuclear γH2AX expression is positively associated with the PD-L1 expression in lung squamous cell carcinoma. (iiarjournals.org)
- In terms of histology, lung squamous cell carcinoma, which accounts for 22% of the cases of resected lung cancer, is associated with poorer overall survival, with a five-year survival rate of approximately 60% in comparison to adenocarcinoma, which is the most common histological type (68%) and which has a five-year survival rate of approximately 75% ( 1 ). (iiarjournals.org)
- Among the various types of lung cancer, lung squamous cell carcinoma has fewer treatment options because it is driven by alterations of tumor suppressor genes and subsequent chromosomal instability rather than oncogenic mutations ( 2 ). (iiarjournals.org)
- Groundbreaking progress has been achieved in the treatment of recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). (dovepress.com)
- Approximately 90% of HNC is head and neck squamous cell carcinoma (HNSCC), with ≈650,000 new cases reported annually worldwide. (dovepress.com)
- HRS cell expression of β2-microglobulin/MHC class I was not predictive for complete remission or PFS after nivolumab therapy. (elsevier.com)
- 12-month interval between myeloablative autologous stem-cell transplantation and nivolumab therapy, HRS cell expression of MHC class II was associated with prolonged PFS. (elsevier.com)
- Initial clinical trial results with IgG4 PD-1 antibody nivolumab (under the brand name Opdivo and developed by Bristol-Myers Squibb) were published in 2010. (wikipedia.org)
- Pembrolizumab and nivolumab, mAbs against PD-1, were FDA-approved in 2014. (biomedcentral.com)
- Those results facilitated pembrolizumab (MK-3475) and nivolumab (BMS-936558), which are antagonists of the PD-1/PD-L1 axis, to become the first molecular-targeted therapeutic drugs to be approved by the US Food and Drug Administration (FDA) for HNSCC. (dovepress.com)
- Pyruvate controls the checkpoint inhibitor PD-L1 and suppresses T cell immunity. (stanford.edu)
- Pembrolizumab (brand name Keytruda) is another PD-1 inhibitor that was approved by the FDA in 2014 and was the second checkpoint inhibitor approved in the United States. (wikipedia.org)
- A lower incidence of hypothyroidism was observed in a trial of combined B cell depletion and immune checkpoint inhibitor treatment compared with studies of immune checkpoint inhibitor monotherapy. (wikipedia.org)
- In a 3 + 3 dose escalation study, 10 patients received pembrolizumab 1, 3, or 10 mg/kg intravenously every 2 weeks until progression or intolerable toxicity. (aacrjournals.org)
- One important family of membrane-bound ligands that bind both co-stimulatory and inhibitory receptors is the B7 family. (nih.gov)
- Of note, other co-inhibitory receptors (BTLA, CTLA-4, TIM-3, LAG-3) are also overexpressed in sepsis. (biomedcentral.com)
- Pegylated IFN-α treatment enhanced recovery of memory T cells in CHB patients by down-regulating inhibitory receptors and up-regulating effector molecules. (biomedcentral.com)
- Siglec-9-expressing T cells coexpressed several inhibitory receptors, including PD-1. (jci.org)
- It appears that (cancer-mediated) upregulation of PD-L1 on the cell surface may inhibit T cells that might otherwise attack. (wikipedia.org)
- A method of reducing an immune response to a transplant in a recipient by treating said recipient with an amount of mesenchymal stem cells effective to reduce or inhibit host rejection of the transplant. (google.com)
- Overexpression of programmed death 1 (PD-1) receptor is thought to inhibit the effector T-cell response in human tuberculosis. (umn.edu)
- The authors hypothesized that these inhibitory molecules inhibit T-cell functions leading to poor viral clearance-a similar consequence to those observed during sepsis-induced immunosuppression. (biomedcentral.com)
- We thus postulate that viral anti-apoptotic factors, known to inhibit suicide of infected host cells, have evolved additional functions to directly abrogate T cell cytotoxicity. (pubmedcentralcanada.ca)
- the anti-CD37 monoclonal antibody allows targeted delivery of the cytotoxic medication to the cancer cell. (dana-farber.org)
- A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1,PCD-1,) with immune checkpoint inhibitory and antineoplastic activities. (cancer.gov)
Regulatory T cel3
- Increased proportion of CD4(+)CD25(+)Foxp3(+) regulatory T cells during the early-stage sepsis in ICU patients. (fichier-pdf.fr)
- Monneret G, Venet F. Additional bad news from regulatory T cells in sepsis. (fichier-pdf.fr)
- Type 2 innate lymphoid cell suppression by regulatory T cells attenuates airway hyperreactivity and requires inducible T-cell costimulator-inducible T-cell costimulator ligand interactionJ Allergy Clin Immunol. (usc.edu)
- 2) PD-1 is also expressed on activated non-T cells, including B cells, natural killer cells, and monocytes, implying that PD-1 may also modulate immunity in a T-cell-independent manner. (thefreelibrary.com)
- We show programmed death ligand-1 (PD-L1) expression on monocytes in the ascites and blood of patients with malignant OC is strikingly higher than those with benign/borderline disease, with no overlap in the values between these groups. (springer.com)
- Both glycosylation variants showed no antibody-mediated lysis of B cells and monocytes. (frontiersin.org)
- Expression of PD-1 and its ligands (PD-L1/L2) on T cells, B cells, and monocytes was evaluated by flow cytometry (FACS). (umn.edu)
- We showed higher frequencies of T cells, monocytes, and B cells expressing PD-1 and its ligand(s) among patients with pulmonary tuberculosis. (umn.edu)
- Secondly, it highlights the importance of monocytes in the PD-1 system and more broadly in sepsis-induced immune alterations. (biomedcentral.com)
- Manipulation of PD-1 signaling may restore the host T-cell response and thus may have therapeutic potential. (umn.edu)
- Their therapeutic effects are highly correlated with recovery of host antiviral immunity. (biomedcentral.com)
- Each NK/T-cell malignancy has its own signature, requiring knowledge of the appropriate diagnostic, prognostic, and therapeutic considerations when caring for afflicted individuals. (cancernetwork.com)