Antigens: Substances that are recognized by the immune system and induce an immune reaction.Antigens, CD: 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.Antigens, CD8: Differentiation antigens found on thymocytes and on cytotoxic and suppressor T-lymphocytes. CD8 antigens are members of the immunoglobulin supergene family and are associative recognition elements in MHC (Major Histocompatibility Complex) Class I-restricted interactions.Antigens, Neoplasm: Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.Antigens, CD3: Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).Antigens, Surface: Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.Antigens, Bacterial: Substances elaborated by bacteria that have antigenic activity.Antigens, CD38: A bifunctional enzyme that catalyzes the synthesis and HYDROLYSIS of CYCLIC ADP-RIBOSE (cADPR) from NAD+ to ADP-RIBOSE. It is a cell surface molecule which is predominantly expressed on LYMPHOID CELLS and MYELOID CELLS.Antigens, CD34: Glycoproteins found on immature hematopoietic cells and endothelial cells. They are the only molecules to date whose expression within the blood system is restricted to a small number of progenitor cells in the bone marrow.Antigens, CD19: Differentiation antigens expressed on B-lymphocytes and B-cell precursors. They are involved in regulation of B-cell proliferation.Antigens, CD40: A member of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. It is found on mature B-LYMPHOCYTES and some EPITHELIAL CELLS, lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations of the gene for CD40 antigen result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.CD40 Ligand: A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.Antigens, CD20: Unglycosylated phosphoproteins expressed only on B-cells. They are regulators of transmembrane Ca2+ conductance and thought to play a role in B-cell activation and proliferation.Antigens, Viral: Substances elaborated by viruses that have antigenic activity.Antigens, CD28: Costimulatory T-LYMPHOCYTE receptors that have specificity for CD80 ANTIGEN and CD86 ANTIGEN. Activation of this receptor results in increased T-cell proliferation, cytokine production and promotion of T-cell survival.Antigens, CD44: Acidic sulfated integral membrane glycoproteins expressed in several alternatively spliced and variable glycosylated forms on a wide variety of cell types including mature T-cells, B-cells, medullary thymocytes, granulocytes, macrophages, erythrocytes, and fibroblasts. CD44 antigens are the principle cell surface receptors for hyaluronate and this interaction mediates binding of lymphocytes to high endothelial venules. (From Abbas et al., Cellular and Molecular Immunology, 2d ed, p156)Antigens, CD7: Differentiation antigens expressed on pluripotential hematopoietic cells, most human thymocytes, and a major subset of peripheral blood T-lymphocytes. They have been implicated in integrin-mediated cellular adhesion and as signalling receptors on T-cells.Antigens, CD14: Glycolipid-anchored membrane glycoproteins expressed on cells of the myelomonocyte lineage including monocytes, macrophages, and some granulocytes. They function as receptors for the complex of lipopolysaccharide (LPS) and LPS-binding protein.Antigens, CD2: Glycoprotein members of the immunoglobulin superfamily which participate in T-cell adhesion and activation. They are expressed on most peripheral T-lymphocytes, natural killer cells, and thymocytes, and function as co-receptors or accessory molecules in the T-cell receptor complex.CD4-CD8 Ratio: Ratio of T-LYMPHOCYTES that express the CD4 ANTIGEN to those that express the CD8 ANTIGEN. This value is commonly assessed in the diagnosis and staging of diseases affecting the IMMUNE SYSTEM including HIV INFECTIONS.Antigens, CD5: Glycoproteins expressed on all mature T-cells, thymocytes, and a subset of mature B-cells. Antibodies specific for CD5 can enhance T-cell receptor-mediated T-cell activation. The B-cell-specific molecule CD72 is a natural ligand for CD5. (From Abbas et al., Cellular and Molecular Immunology, 2d ed, p156)Antigens, Differentiation: Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.CD4-Positive T-Lymphocytes: 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.Antigens, CD1: Glycoproteins expressed on cortical thymocytes and on some dendritic cells and B-cells. Their structure is similar to that of MHC Class I and their function has been postulated as similar also. CD1 antigens are highly specific markers for human LANGERHANS CELLS.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Antigens, CD56: The 140 kDa isoform of NCAM (neural cell adhesion molecule) containing a transmembrane domain and short cytoplasmic tail. It is expressed by all lymphocytes mediating non-MHC restricted cytotoxicity and is present on some neural tissues and tumors.Antigens, Differentiation, T-Lymphocyte: Antigens expressed on the cell membrane of T-lymphocytes during differentiation, activation, and normal and neoplastic transformation. Their phenotypic characterization is important in differential diagnosis and studies of thymic ontogeny and T-cell function.ADP-ribosyl Cyclase: A membrane-bound or cytosolic enzyme that catalyzes the synthesis of CYCLIC ADP-RIBOSE (cADPR) from nicotinamide adenine dinucleotide (NAD). This enzyme generally catalyzes the hydrolysis of cADPR to ADP-RIBOSE, as well, and sometimes the synthesis of cyclic ADP-ribose 2' phosphate (2'-P-cADPR) from NADP.Antigens, Differentiation, Myelomonocytic: Surface antigens expressed on myeloid cells of the granulocyte-monocyte-histiocyte series during differentiation. Analysis of their reactivity in normal and malignant myelomonocytic cells is useful in identifying and classifying human leukemias and lymphomas.Antigens, CD80: 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.Antigens, CD53: Tetraspanin proteins found at high levels in cells of the lymphoid-myeloid lineage. CD53 antigens may be involved regulating the differentiation of T-LYMPHOCYTES and the activation of B-LYMPHOCYTES.Antigens, CD24: A cell adhesion protein that was originally identified as a heat stable antigen in mice. It is involved in METASTASIS and is highly expressed in many NEOPLASMS.Antigens, CD13: Zinc-binding metalloproteases that are members of the type II integral membrane metalloproteases. They are expressed by GRANULOCYTES; MONOCYTES; and their precursors as well as by various non-hematopoietic cells. They release an N-terminal amino acid from a peptide, amide or arylamide.Antigens, Protozoan: Any part or derivative of any protozoan that elicits immunity; malaria (Plasmodium) and trypanosome antigens are presently the most frequently encountered.T-Lymphocytes: 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.Antigens, CD86: A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CD28 ANTIGEN with high specificity and to CTLA-4 ANTIGEN with low specificity. The interaction of CD86 with CD28 ANTIGEN provides a stimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.Flow Cytometry: 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.B-Lymphocytes: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.Antigens, Polyomavirus Transforming: Polyomavirus antigens which cause infection and cellular transformation. The large T antigen is necessary for the initiation of viral DNA synthesis, repression of transcription of the early region and is responsible in conjunction with the middle T antigen for the transformation of primary cells. Small T antigen is necessary for the completion of the productive infection cycle.Antigens, CD95: 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.HLA Antigens: Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.Antigens, Differentiation, B-Lymphocyte: Membrane antigens associated with maturation stages of B-lymphocytes, often expressed in tumors of B-cell origin.Antigens, CD45: High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.Immunophenotyping: Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.NAD+ NucleosidaseAntigens, Fungal: Substances of fungal origin that have antigenic activity.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.H-2 Antigens: The major group of transplantation antigens in the mouse.Sialic Acid Binding Ig-like Lectin 3: A 67-kDa sialic acid binding lectin that is specific for MYELOID CELLS and MONOCYTE-MACROPHAGE PRECURSOR CELLS. This protein is the smallest siglec subtype and contains a single immunoglobulin C2-set domain. It may play a role in intracellular signaling via its interaction with SHP-1 PROTEIN-TYROSINE PHOSPHATASE and SHP-2 PROTEIN-TYROSINE PHOSPHATASE.Antigens, Helminth: Any part or derivative of a helminth that elicits an immune reaction. The most commonly seen helminth antigens are those of the schistosomes.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.Antigens, CD18: Cell-surface glycoprotein beta-chains that are non-covalently linked to specific alpha-chains of the CD11 family of leukocyte-adhesion molecules (RECEPTORS, LEUKOCYTE-ADHESION). A defect in the gene encoding CD18 causes LEUKOCYTE-ADHESION DEFICIENCY SYNDROME.Lymphocyte Activation: 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.Antigens, CD30: A member of the tumor necrosis factor receptor superfamily that may play a role in the regulation of NF-KAPPA B and APOPTOSIS. They are found on activated T-LYMPHOCYTES; B-LYMPHOCYTES; NEUTROPHILS; EOSINOPHILS; MAST CELLS and NK CELLS. Overexpression of CD30 antigen in hematopoietic malignancies make the antigen clinically useful as a biological tumor marker. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.CD8-Positive T-Lymphocytes: A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.Epitopes: Sites on an antigen that interact with specific antibodies.Antigens, CD9: A subtype of tetraspanin proteins that play a role in cell adhesion, cell motility, and tumor metastasis. CD9 antigens take part in the process of platelet activation and aggregation, the formation of paranodal junctions in neuronal tissue, and the fusion of sperm with egg.Carcinoembryonic Antigen: A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the response to colon cancer treatment.HLA-DR Antigens: A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS.Antigens, CD15: A trisaccharide antigen expressed on glycolipids and many cell-surface glycoproteins. In the blood the antigen is found on the surface of NEUTROPHILS; EOSINOPHILS; and MONOCYTES. In addition, CD15 antigen is a stage-specific embryonic antigen.Antigens, Viral, Tumor: Those proteins recognized by antibodies from serum of animals bearing tumors induced by viruses; these proteins are presumably coded for by the nucleic acids of the same viruses that caused the neoplastic transformation.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Antigens, CD43: A sialic acid-rich protein and an integral cell membrane mucin. It plays an important role in activation of T-LYMPHOCYTES.Antigens, CD36: Leukocyte differentiation antigens and major platelet membrane glycoproteins present on MONOCYTES; ENDOTHELIAL CELLS; PLATELETS; and mammary EPITHELIAL CELLS. They play major roles in CELL ADHESION; SIGNAL TRANSDUCTION; and regulation of angiogenesis. CD36 is a receptor for THROMBOSPONDINS and can act as a scavenger receptor that recognizes and transports oxidized LIPOPROTEINS and FATTY ACIDS.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Antigens, CD11: A group of three different alpha chains (CD11a, CD11b, CD11c) that are associated with an invariant CD18 beta chain (ANTIGENS, CD18). The three resulting leukocyte-adhesion molecules (RECEPTORS, LEUKOCYTE ADHESION) are LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1; MACROPHAGE-1 ANTIGEN; and ANTIGEN, P150,95.Histocompatibility Antigens Class II: Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.Histocompatibility Antigens: A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection.Antigens, CD59: Small glycoproteins found on both hematopoietic and non-hematopoietic cells. CD59 restricts the cytolytic activity of homologous complement by binding to C8 and C9 and blocking the assembly of the membrane attack complex. (From Barclay et al., The Leukocyte Antigen FactsBook, 1993, p234)Receptors, Antigen, B-Cell: IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.Proliferating Cell Nuclear Antigen: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.Antigens, CD57: Oligosaccharide antigenic determinants found principally on NK cells and T-cells. Their role in the immune response is poorly understood.Antigens, CD70: A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds to CD27 ANTIGEN. It is found on activated T-LYMPHOCYTES; B-LYMPHOCYTES; and DENDRITIC CELLS where it plays a role in stimulating the proliferation of CD4-POSITIVE T-LYMPHOCYTES and CD8-POSITIVE T-LYMPHOCYTES.Antigens, CD46: A ubiquitously expressed complement receptor that binds COMPLEMENT C3B and COMPLEMENT C4B and serves as a cofactor for their inactivation. CD46 also interacts with a wide variety of pathogens and mediates immune response.Lectins, C-Type: A class of animal lectins that bind to carbohydrate in a calcium-dependent manner. They share a common carbohydrate-binding domain that is structurally distinct from other classes of lectins.Antigens, CD58: Glycoproteins with a wide distribution on hematopoietic and non-hematopoietic cells and strongly expressed on macrophages. CD58 mediates cell adhesion by binding to CD2; (ANTIGENS, CD2); and this enhances antigen-specific T-cell activation.Antigens, CD4: 55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. CD4 antigens are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. CD4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120.Antigens, CD47: A ubiquitously expressed membrane glycoprotein. It interacts with a variety of INTEGRINS and mediates responses to EXTRACELLULAR MATRIX PROTEINS.Antigens, CD11b: A CD antigen that contains a conserved I domain which is involved in ligand binding. When combined with CD18 the two subunits form MACROPHAGE-1 ANTIGEN.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Prostate-Specific Antigen: A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.Antigens, CD11c: An integrin alpha subunit of approximately 150-kDa molecular weight. It is expressed at high levels on monocytes and combines with CD18 ANTIGEN to form the cell surface receptor INTEGRIN ALPHAXBETA2. The subunit contains a conserved I-domain which is characteristic of several of alpha integrins.O Antigens: The lipopolysaccharide-protein somatic antigens, usually from gram-negative bacteria, important in the serological classification of enteric bacilli. The O-specific chains determine the specificity of the O antigens of a given serotype. O antigens are the immunodominant part of the lipopolysaccharide molecule in the intact bacterial cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)HLA-A2 Antigen: A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*02 allele family.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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive.CD4 Lymphocyte Count: The number of CD4-POSITIVE T-LYMPHOCYTES per unit volume of BLOOD. Determination requires the use of a fluorescence-activated flow cytometer.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Cell SeparationAntigens, Tumor-Associated, Carbohydrate: Carbohydrate antigens expressed by malignant tissue. They are useful as tumor markers and are measured in the serum by means of a radioimmunoassay employing monoclonal antibodies.Antigens, CD55: GPI-linked membrane proteins broadly distributed among hematopoietic and non-hematopoietic cells. CD55 prevents the assembly of C3 CONVERTASE or accelerates the disassembly of preformed convertase, thus blocking the formation of the membrane attack complex.Antigens, CD31: Cell adhesion molecules present on virtually all monocytes, platelets, and granulocytes. CD31 is highly expressed on endothelial cells and concentrated at the junctions between them.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.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.Antigens, CD81: Tetraspanin proteins that are involved in a variety of cellular functions including BASEMENT MEMBRANE assembly, and in the formation of a molecular complexes on the surface of LYMPHOCYTES.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Antigens, CD137: A member of the tumor necrosis factor receptor superfamily that is specific for 4-1BB LIGAND. It is found in a variety of immune cell types including activated T-LYMPHOCYTES; NATURAL KILLER CELLS; and DENDRITIC CELLS. Activation of the receptor on T-LYMPHOCYTES plays a role in their expansion, production of cytokines and survival. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.Mice, Inbred BALB CMonocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.HLA-A Antigens: Polymorphic class I human histocompatibility (HLA) surface antigens present on almost all nucleated cells. At least 20 antigens have been identified which are encoded by the A locus of multiple alleles on chromosome 6. They serve as targets for T-cell cytolytic responses and are involved with acceptance or rejection of tissue/organ grafts.Cross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.Dendritic Cells: 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).Receptors, Interleukin-2: Receptors present on activated T-LYMPHOCYTES and B-LYMPHOCYTES that are specific for INTERLEUKIN-2 and play an important role in LYMPHOCYTE ACTIVATION. They are heterotrimeric proteins consisting of the INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT, the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT, and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN.Blood Group Antigens: Sets of cell surface antigens located on BLOOD CELLS. They are usually membrane GLYCOPROTEINS or GLYCOLIPIDS that are antigenically distinguished by their carbohydrate moieties.Hepatitis B Surface Antigens: Those hepatitis B antigens found on the surface of the Dane particle and on the 20 nm spherical and tubular particles. Several subspecificities of the surface antigen are known. These were formerly called the Australia antigen.Antigens, CD63: Ubiquitously-expressed tetraspanin proteins that are found in late ENDOSOMES and LYSOSOMES and have been implicated in intracellular transport of proteins.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.Antigens, CD151: Tetraspanin proteins found associated with LAMININ-binding INTEGRINS. The CD151 antigens may play a role in the regulation of CELL MOTILITY.Antigens, CD79: A component of the B-cell antigen receptor that is involved in B-cell antigen receptor heavy chain transport to the PLASMA MEMBRANE. It is expressed almost exclusively in B-LYMPHOCYTES and serves as a useful marker for B-cell NEOPLASMS.Spleen: An encapsulated lymphatic organ through which venous blood filters.Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.HLA-D Antigens: Human immune-response or Class II antigens found mainly, but not exclusively, on B-lymphocytes and produced from genes of the HLA-D locus. They are extremely polymorphic families of glycopeptides, each consisting of two chains, alpha and beta. This group of antigens includes the -DR, -DQ and -DP designations, of which HLA-DR is most studied; some of these glycoproteins are associated with certain diseases, possibly of immune etiology.CD30 Ligand: A membrane-bound tumor necrosis family member found primarily on activated T-LYMPHOCYTES that binds specifically to CD30 ANTIGEN. It may play a role in INFLAMMATION and immune regulation.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.N-Glycosyl Hydrolases: A class of enzymes involved in the hydrolysis of the N-glycosidic bond of nitrogen-linked sugars.Burkitt Lymphoma: A form of undifferentiated malignant LYMPHOMA usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (HERPESVIRUS 4, HUMAN) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative.Receptors, Antigen: Molecules on the surface of B- and T-lymphocytes that recognize and combine with specific antigens.Immunization: Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Antigens, CD11a: An alpha-integrin subunit found on lymphocytes, granulocytes, macrophages and monocytes. It combines with the integrin beta2 subunit (CD18 ANTIGEN) to form LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1.RNA, Messenger: 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.Hepatitis B Antigens: Antigens of the virion of the HEPATITIS B VIRUS or the Dane particle, its surface (HEPATITIS B SURFACE ANTIGENS), core (HEPATITIS B CORE ANTIGENS), and other associated antigens, including the HEPATITIS B E ANTIGENS.Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Antigen-Antibody Reactions: The processes triggered by interactions of ANTIBODIES with their ANTIGENS.Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.Macrophages: 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.)Mice, SCID: 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.T-Lymphocytes, Cytotoxic: 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.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Antigen-Presenting Cells: 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.Herpesvirus 4, Human: The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies.Receptors, Antigen, T-Cell, alpha-beta: T-cell receptors composed of CD3-associated alpha and beta polypeptide chains and expressed primarily in CD4+ or CD8+ T-cells. Unlike immunoglobulins, the alpha-beta T-cell receptors recognize antigens only when presented in association with major histocompatibility (MHC) molecules.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.HLA-B Antigens: Class I human histocompatibility (HLA) surface antigens encoded by more than 30 detectable alleles on locus B of the HLA complex, the most polymorphic of all the HLA specificities. Several of these antigens (e.g., HLA-B27, -B7, -B8) are strongly associated with predisposition to rheumatoid and other autoimmune disorders. Like other class I HLA determinants, they are involved in the cellular immune reactivity of cytolytic T lymphocytes.Immunologic Memory: The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus.Bone Marrow Cells: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.Cytotoxicity, Immunologic: The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.MART-1 Antigen: A melanosome-specific protein that plays a role in the expression, stability, trafficking, and processing of GP100 MELANOMA ANTIGEN, which is critical to the formation of Stage II MELANOSOMES. The protein is used as an antigen marker for MELANOMA cells.Antigens, CD147: A widely distributed cell surface transmembrane glycoprotein that stimulates the synthesis of MATRIX METALLOPROTEINASES. It is found at high levels on the surface of malignant NEOPLASMS and may play a role as a mediator of malignant cell behavior.Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.Mice, Inbred C57BLOvalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily.HIV Antigens: Antigens associated with specific proteins of the human adult T-cell immunodeficiency virus (HIV); also called HTLV-III-associated and lymphadenopathy-associated virus (LAV) antigens.CTLA-4 Antigen: An inhibitory T CELL receptor that is closely related to CD28 ANTIGEN. It has specificity for CD80 ANTIGEN and CD86 ANTIGEN and acts as a negative regulator of peripheral T cell function. CTLA-4 antigen is believed to play role in inducing PERIPHERAL TOLERANCE.HL-60 Cells: A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)Antigens, CD82: A widely expressed transmembrane glycoprotein that functions as a METASTASIS suppressor protein. It is underexpressed in a variety of human NEOPLASMS.Immunoenzyme Techniques: Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Antigens, Thy-1: A group of differentiation surface antigens, among the first to be discovered on thymocytes and T-lymphocytes. Originally identified in the mouse, they are also found in other species including humans, and are expressed on brain neurons and other cells.Cytokines: 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.Immune Tolerance: 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.Immunity, Cellular: Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.Thymus Gland: A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.Autoantigens: Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.Clone Cells: 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)Epstein-Barr Virus Nuclear Antigens: Nuclear antigens encoded by VIRAL GENES found in HUMAN HERPESVIRUS 4. At least six nuclear antigens have been identified.Interleukin-2: A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.Immunoglobulin M: A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.Cell Line, Tumor: A cell line derived from cultured tumor cells.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.H-Y Antigen: A sex-specific cell surface antigen produced by the sex-determining gene of the Y chromosome in mammals. It causes syngeneic grafts from males to females to be rejected and interacts with somatic elements of the embryologic undifferentiated gonad to produce testicular organogenesis.Antigens, CD146: A cell adhesion molecule of the immunoglobulin superfamily that is expressed in ENDOTHELIAL CELLS and is involved in INTERCELLULAR JUNCTIONS.Antigens, Heterophile: Antigens stimulating the formation of, or combining with heterophile antibodies. They are cross-reacting antigens found in phylogenetically unrelated species.T-Lymphocytes, Regulatory: CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.Antibodies, Monoclonal, Murine-Derived: Antibodies obtained from a single clone of cells grown in mice or rats.Epitopes, T-Lymphocyte: Antigenic determinants recognized and bound by the T-cell receptor. Epitopes recognized by the T-cell receptor are often located in the inner, unexposed side of the antigen, and become accessible to the T-cell receptors after proteolytic processing of the antigen.Interferon-gamma: 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.Antigens, CD98: A heterodimeric protein that is a cell surface antigen associated with lymphocyte activation. The initial characterization of this protein revealed one identifiable heavy chain (ANTIGENS, CD98 HEAVY CHAIN) and an indeterminate smaller light chain. It is now known that a variety of light chain subunits (ANTIGENS, CD98 LIGHT CHAINS) can dimerize with the heavy chain. Depending upon its light chain composition a diverse array of functions can be found for this protein. Functions include: type L amino acid transport, type y+L amino acid transport and regulation of cellular fusion.Hepatitis B Core Antigens: The hepatitis B antigen within the core of the Dane particle, the infectious hepatitis virion.Peptides: 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.Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.Lymph Nodes: They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.Molecular Weight: The sum of the weight of all the atoms in a molecule.Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.HLA-DQ Antigens: A group of the D-related HLA antigens found to differ from the DR antigens in genetic locus and therefore inheritance. These antigens are polymorphic glycoproteins comprising alpha and beta chains and are found on lymphoid and other cells, often associated with certain diseases.Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.Signal Transduction: 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.Mice, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.Forssman Antigen: A glycolipid, cross-species antigen that induces production of antisheep hemolysin. It is present on the tissue cells of many species but absent in humans. It is found in many infectious agents.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Antigens, CD274: An inhibitory B7 antigen that has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 PROTEIN. CD274 antigen provides negative signals that control and inhibit T-cell responses and is found at higher than normal levels on tumor cells, suggesting its potential role in TUMOR IMMUNE EVASION.Complement Fixation Tests: Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.Simian virus 40: A species of POLYOMAVIRUS originally isolated from Rhesus monkey kidney tissue. It produces malignancy in human and newborn hamster kidney cell cultures.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Adjuvants, Immunologic: 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.Isoantigens: Antigens that exist in alternative (allelic) forms in a single species. When an isoantigen is encountered by species members who lack it, an immune response is induced. Typical isoantigens are the BLOOD GROUP ANTIGENS.Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure MONOCLONAL ANTIBODIES or T-cell products, identical to those produced by the immunologically competent parent cell.gp100 Melanoma Antigen: A melanosome-associated protein that plays a role in the maturation of the MELANOSOME.Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.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.Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.

B7-H1 costimulation preferentially enhances CD28-independent T-helper cell function. (1/481)

B7-H1 is a recently described B7-like molecule that costimulates T-cell growth and cytokine secretion without binding to CD28, cytotoxic T-lymphocyte antigen-4 (CTLA-4), and inducible costimulator (ICOS). In this report, a mouse homologue of human B7-H1 is identified, and its immunologic functions are studied in vitro and in vivo. Mouse B7-H1 shares 69% amino acid homology to the human counterpart. Similar to human B7-H1, mouse B7-H1 can be induced to express on macrophages, T cells, and B cells and to enhance T-cell proliferation and secretion of interleukin-10 (IL-10), interferon-gamma, and granulocyte-macrophage colony-stimulating factor but not IL-2 and IL-4. Furthermore, B7-H1 preferentially costimulates CD4+ T cells independently of CD28 and enhances mixed lymphocyte responses to allogeneic antigens. In contrast to B7-1, expression of B7-H1 on murine P815 tumor cells by transfection fails to increase allogeneic and syngeneic cytolytic T-cell responses in vitro and in vivo. Administration of B7-H1Ig fusion protein, however, enhances keyhole limpet hemocyanin- specific T-cell proliferation and 2,4,6-trinitrophenyl-specific immunoglobulin G2a antibody production. The study thus identifies a unique costimulatory pathway that preferentially affects T-helper cell functions.  (+info)

CD4+CD25high regulatory cells in human peripheral blood. (2/481)

Thymectomy in mice on neonatal day 3 leads to the development of multiorgan autoimmune disease due to loss of a CD(+)CD25(+) T cell regulatory population in their peripheral lymphoid tissues. Here, we report the identification of a CD4(+) population of regulatory T cells in the circulation of humans expressing high levels of CD25 that exhibit in vitro characteristics identical with those of the CD4(+)CD25(+) regulatory cells isolated in mice. With TCR cross-linking, CD4(+)CD25(high) cells did not proliferate but instead totally inhibited proliferation and cytokine secretion by activated CD4(+)CD25(-) responder T cells in a contact-dependent manner. The CD4(+)CD25(high) regulatory T cells expressed high levels of CD45RO but not CD45RA, akin to the expression of CD45RB(low) on murine CD4(+)CD25(+) regulatory cells. Increasing the strength of signal by providing either costimulation with CD28 cross-linking or the addition of IL-2 to a maximal anti-CD3 stimulus resulted in a modest induction of proliferation and the loss of observable suppression in cocultures of CD4(+)CD25(high) regulatory cells and CD4(+)CD25(-) responder cells. Whereas higher ratios of CD4(+)CD25(high) T cells are required to suppress proliferation if the PD-L1 receptor is blocked, regulatory cell function is shown to persist in the absence of the PD-1/PD-L1 or CTLA-4/B7 pathway. Thus, regulatory CD4 T cells expressing high levels of the IL-2 receptor are present in humans, providing the opportunity to determine whether alterations of these populations of T cells are involved in the induction of human autoimmune disorders.  (+info)

Expression and regulation of the PD-L1 immunoinhibitory molecule on microvascular endothelial cells. (3/481)

OBJECTIVE: To evaluate the expression and regulation of a novel B7-like protein, PD-L1, the ligand for the immunoinhibitory receptor PD-1 expressed on activated T-cells, on microvascular endothelial cells (ECs) METHODS: PD-L1 expression on ECs in vitro and in vivo was quantified by using a dual radiolabeled antibody technique after treatment with interferons (IFN) and IL-12, respectively. Changes in the level of PD-L1 mRNA were determined by using RT-PCR. RESULTS: PD-L1 was observed to be present on ECs under basal conditions. Treatment of ECs with IFN-alpha, -beta and -gamma, but not LPS, was observed to induce elevations in the mRNA and surface expression of PD-L1 on ECs. By using a dual radiolabeled monoclonal antibody (mAb) technique, PD-L1 expression in various tissues of control and IL-12 challenged wild-type and IFN-gamma-deficient mice was measured. A significant increase in PD-L1 expression was observed in tissues at 24 hours after IL-12-challenge, with peak levels of PD-L1 occurring 72 hours after IL-12 challenge. IL-12 was not effective at inducing PD-L1 expression in tissues of IFN-gamma-deficient mice. CONCLUSIONS: These data show the expression of a novel B7-like molecule on murine ECs that is mediated by IFN-alpha, -beta, and -gamma, and suggest a potential pathway by which ECs may modulate T-cell function.  (+info)

Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. (4/481)

PD-1 is a receptor of the Ig superfamily that negatively regulates T cell antigen receptor signaling by interacting with the specific ligands (PD-L) and is suggested to play a role in the maintenance of self-tolerance. In the present study, we examined possible roles of the PD-1/PD-L system in tumor immunity. Transgenic expression of PD-L1, one of the PD-L, in P815 tumor cells rendered them less susceptible to the specific T cell antigen receptor-mediated lysis by cytotoxic T cells in vitro, and markedly enhanced their tumorigenesis and invasiveness in vivo in the syngeneic hosts as compared with the parental tumor cells that lacked endogenous PD-L. Both effects could be reversed by anti-PD-L1 Ab. Survey of murine tumor lines revealed that all of the myeloma cell lines examined naturally expressed PD-L1. Growth of the myeloma cells in normal syngeneic mice was inhibited significantly albeit transiently by the administration of anti-PD-L1 Ab in vivo and was suppressed completely in the syngeneic PD-1-deficient mice. These results suggest that the expression of PD-L1 can serve as a potent mechanism for potentially immunogenic tumors to escape from host immune responses and that blockade of interaction between PD-1 and PD-L may provide a promising strategy for specific tumor immunotherapy.  (+info)

B7-H1 is expressed by human endothelial cells and suppresses T cell cytokine synthesis. (5/481)

Human endothelial cells (ECs) provide costimulatory signals sufficient to activate resting memory T cells to produce IL-2 and IFN-gamma, at least in part through CD58-CD2 interactions. Recently, the B7-like molecule, B7-H1 (PD-L1), was described and shown to regulate T cell activation; however, there are conflicting reports on whether it stimulates or inhibits T cell cytokine synthesis. B7-H1 is not expressed constitutively by ECs; however, it is rapidly induced by IFN-gamma, and synergistically by IFN-gamma and TNF. In inflamed skin, B7-H1 is expressed by a subset of microvessels, and by keratinocytes, but is barely detectable in normal skin. Blocking the interaction of EC-expressed B7-H1 with its T cell ligand, programmed death-1 (PD-1), using a PD-1-Fc fusion protein, or by blocking B7-H1 expression with morpholino antisense oligonucleotides, augments expression of IL-2 and IFN-gamma, implicating B7-H1 as a negative regulator of cytokine synthesis. However, signaling through PD-1 does not affect induction of the activation markers CD25 or CD69 on T cells, suggesting that its effects are specific to cytokine synthesis. The suppressive effects of B7-H1 on cytokine expression are proportional to the strength of the primary stimulus, allowing for B7-H1 to determine the level of T cell activation in response to ECs. Our results demonstrate that B7-H1 negatively regulates cytokine synthesis in T cells activated by ECs.  (+info)

Expression of programmed death 1 ligands by murine T cells and APC. (6/481)

Programmed death 1 (PD-1) is a new member of the CD28/CTLA-4 family, which has been implicated in the maintenance of peripheral tolerance. Two ligands for PD-1, namely, B7-H1 (PD-L1) and B7-DC (PD-L2), have recently been identified as new members of the B7 family but their expression at the protein level remains largely unknown. To characterize the expression of B7-H1 and B7-DC, we newly generated an anti-mouse B7-H1 mAb (MIH6) and an anti-mouse B7-DC mAb (TY25). MIH6 and TY25 immunoprecipitated a single molecule of 43 and 42 kDa from the lysate of B7-H1 and B7-DC transfectants, respectively. Flow cytometric analysis revealed that B7-H1 was broadly expressed on the surface of mouse tumor cell lines while the expression of B7-DC was rather restricted. PD-1 was expressed on anti-CD3-stimulated T cells and anti-IgM plus anti-CD40-stimulated B cells at high levels but was undetectable on activated macrophages or DCs. B7-H1 was constitutively expressed on freshly isolated splenic T cells, B cells, macrophages, and dendritic cells (DCs), and up-regulated on T cells by anti-CD3 stimulation on macrophages by LPS, IFN-gamma, GM-CSF, or IL-4, and on DCs by IFN-gamma, GM-CSF, or IL-4. In contrast, B7-DC expression was only inducible on macrophages and DCs upon stimulation with IFN-gamma, GM-CSF, or IL-4. The inducible expression of PD-1 ligands on both T cells and APCs may suggest new paradigms of PD-1-mediated immune regulation.  (+info)

Programmed death-1 targeting can promote allograft survival. (7/481)

The recently identified CD28 homolog and costimulatory molecule programmed death-1 (PD-1) and its ligands, PD-L1 and PD-L2, which are homologs of B7, constitute an inhibitory regulatory pathway of potential therapeutic use in immune-mediated diseases. We examined the expression and functions of PD-1 and its ligands in experimental cardiac allograft rejection. In initial studies, we found that most normal tissues and cardiac isografts had minimal expression of PD-1, PD-L1, or PD-L2, but intragraft induction of all three molecules occurred during development of cardiac allograft rejection. Intragraft expression of all three genes was maintained despite therapy with cyclosporin A or rapamycin, but was prevented in the early posttransplant period by costimulation blockade using CD154 or anti-inducible costimulator mAb. We prepared PD-L1.Ig and PD-L2.Ig fusion proteins and showed that each bound to activated PD-1(+) T cells and inhibited T cell functions in vitro, thereby allowing us to test the effects of PD-1 targeting on allograft survival in vivo. Neither agent alone modulated allograft rejection in wild-type recipients. However, use of PD-L1.Ig administration in CD28(-/-) recipients, or in conjunction with immunosuppression in fully MHC-disparate combinations, markedly prolonged cardiac allograft survival, in some cases causing permanent engraftment, and was accompanied by reduced intragraft expression of IFN-gamma and IFN-gamma-induced chemokines. PD-L1.Ig use also prevented development of transplant arteriosclerosis post-CD154 mAb therapy. These data show that when combined with limited immunosuppression, or in the context of submaximal TCR or costimulatory signals, targeting of PD-1 can block allograft rejection and modulate T and B cell-dependent pathologic immune responses in vivo.  (+info)

B7-H1 is up-regulated in HIV infection and is a novel surrogate marker of disease progression. (8/481)

The ligation of programmed death-ligand 1 (B7-H1) to T cells results in the preferential production of interleukin 10 (IL-10). We investigated if B7-H1 would be up-regulated in HIV infection, a disease characterized by increased IL-10 production, by measuring B7-H1, B7-1 (CD80), and B7-2 (CD86) expression and mRNA in 36 HIV-infected patients and in 22 healthy controls (HCs). Results showed that (1) B7-H1 expression and mRNA are augmented in cells of HIV patients; (2) increased IL-10 production in these patients is largely induced by B7-H1-expressing CD14(+) cells; (3) an inverse correlation is detected between B7-H1 expression and CD4 counts, whereas the up-regulation of B7-H1 is directly associated with HIV plasma viremia; (4) antiviral therapy results in the parallel down modulation of IL-10 production and B7-H1 expression/synthesis; and (5) B7-H1/CD80 and B7-H1/CD86 mRNA ratios are increased in peripheral blood mononuclear cells (PBMCs) of HIV patients compared with HCs. B7-H1 synthesis and expression are up-regulated in HIV infection, and the degree of dysregulation correlates with the severity of disease. Aberrant antigen presentation by antigen-presenting cells (APCs) that exhibit increased B7-H1 expression and IL-10 production in HIV infection could be responsible for T-lymphocyte unresponsiveness and loss of protective immunity. B7-H1 is a surrogate marker potentially involved in AIDS disease progression.  (+info)

*Cancer immunotherapy

Dendritic cells are antigen presenting cells (APCs) in the mammalian immune system. In cancer treatment they aid cancer antigen ... Cell surface receptors are common targets for antibody therapies and include CD20, CD274 and CD279. Once bound to a cancer ... Cancer vaccine Antigen 5T4 Chimeric antigen receptor Coley's Toxins Combinatorial ablation and immunotherapy Cryoimmunotherapy ... Antigens can be added to the antibody and can induce the dendritic cells to mature and provide immunity to the tumor. Dendritic ...

*PD-L1

CD274 CD274 molecule". Chemnitz JM, Parry RV, Nichols KE, June CH, Riley JL (July 2004). "SHP-1 and SHP-2 associate with ... Normally the immune system reacts to foreign antigens that are associated with exogenous or endogenous Danger signals, which ... Programmed death-ligand 1 (PD-L1) also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1) is a protein ... CD274 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH). ...

*Immunoglobulin V-set domain

CD274; CD276; CD300A; CD300C; CD300D; CD300E; CD300LB; CD300LF; CD300LG; CD33; CD3G; CD7; CD79A; CD79B; CD80; CD83; CD86; CD8A ... IPR003596 T-cell surface antigen CD2 InterPro: IPR013285 ACAM; ACAN; ADAMTSL1; AGC1; AMICA1; BCAM; BCAN; BGP; BGPc; BT3.3; ...

*Checkpoint inhibitor

Cancer immunotherapy Chimeric antigen receptor Pardoll DM (March 2012). "The blockade of immune checkpoints in cancer ... CD274). PD-L1 on the cell surface binds to PD1 on an immune cell surface, which inhibits immune cell activity. Among PD-L1 ...
Free Online Library: Programmed Death Ligand-1 (PD-L1) Expression in the Programmed Death Receptor-1 (PD-1)/PD-L1 Blockade: A Key Player Against Various Cancers.(Report) by Archives of Pathology & Laboratory Medicine; Health, general Apoptosis Research Gene expression
A Molecular Epidemiological Analysis Of Programmed Cell Death Ligand-1 (PD-L1) Protein Expression, Mutations And Survival In Non-Small Cell Lung Cancer
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El Annan J, Goyal S, Zhang Q, Freeman GJ, Sharpe AH, Dana R. Regulation of T-cell chemotaxis by programmed death-ligand 1 (PD-L1) in dry eye-associated corneal inflammation. Invest Ophthalmol Vis Sci. 2010;51 (7) :3418-23.
Programmed cell death ligand-1 (PD-L1) plays a pivotal role in the suppression of antitumour immunity by binding to programmed cell death-1 (PD-1) on tumouricidal cytotoxic T lymphocytes (CTLs), rendering them inactive. As blockade of PD-1/PD-L1 interaction by the monoclonal antibodies induced effective T cell-mediated antitumour response, suppression of PD-L1 expression in tumour cells by the chemical agent might contribute to treatment against malignant tumours. Nafamostat mesilate (NM), a serine protease inhibitor that is frequently used in the clinic, potently suppressed interferon-gamma (IFN-gamma)-induced up-regulation of PD-L1 in cultured human lung cancer cells (HLC-1) at both the messenger RNA (mRNA) and protein levels ...
CD274 / PD-L1 (programmed death ligand-1), also known as B7-H1, is a member of the B7 family of regulatory proteins. It can act as both costimulatory and coinhibitory molecule for T cells. Interaction with its ligand CD279 (PD1) appears to be important in the maintenance of peripheral tolerance and in prevention of tumor rejection. Even pathogens (e.g. Schistosoma) may exploit CD274 to evade an immune response. Besides CD279, existence of other receptor(s) for CD274 is likely ...
Programmed death-1-directed (PD-1-directed) immune checkpoint blockade results in durable antitumor activity in many advanced malignancies. Recent studies suggest that IFN-γ is a critical driver of programmed death ligand-1 (PD-L1) expression in cancer and host cells, and baseline intratumoral T cell infiltration may improve response likelihood to anti-PD-1 therapies, including pembrolizumab. However, whether quantifying T cell-inflamed microenvironment is a useful pan-tumor determinant of PD-1-directed therapy response has not been rigorously evaluated. Here, we analyzed gene expression profiles (GEPs) using RNA from baseline tumor samples of pembrolizumab-treated patients. We identified immune-related signatures correlating with clinical benefit using a learn-and-confirm paradigm based on data from different clinical studies of pembrolizumab, starting with a small pilot of 19 melanoma patients and eventually defining a pan-tumor T cell-inflamed GEP in 220 patients with 9 cancers. Predictive ...
The authors identify programmed cell death ligand-1 (PD-L1), an immunity suppressor produced by cancer cells, as a new pain inhibitor and a neuromodulator. They report that PD-L1 is produced by melanoma and normal neural tissues and that it inhibits acute and chronic pain. Via activation of PD-1, its receptor, PD-L1 decreases the excitability of nociceptive neurons in mouse and human dorsal root ganglia. ...
Programmed death-1 (PD-1) is a receptor on T cells that has been shown to suppress activating signals from the T cell receptor when bound by either of its ligands, Programmed death-ligand 1 (PD-L1) or PD-L2. When PD-1 expressing T cells contact cells expressing its ligands, functional activities in response to antigenic stimuli, including proliferation, cytokine secretion, and cytotoxicity are reduced. PD-1/PD-Ligand interactions down regulate immune responses during resolution of an infection or tumor, or during the development of self tolerance.. Interference with the PD-1/PD-L1 interaction has also shown enhanced T cell activity in chronic infection systems. Chronic lymphocytic chorio meningitis virus infection of mice also exhibits improved virus clearance and restored immunity with blockade of PD-L1.. In addition to enhancing immunologic responses to chronic antigens, blockade of the PD-1/PD-L1 pathway has also been shown to enhance responses to vaccination, including therapeutic ...
SP263 : Programmed cell death 1-ligand 1 (PD-L1), also known as B7 homolog 1 (B7-H1) or CD274, is a transmembrane protein involved in the regulation of cell-mediated immune responses through interaction with the receptor programmed death protein-1 (PD-1). PD-L1 has been identified as both a prognostic and theranostic marker in a variety of neoplasms. Overexpression of PD-L1 has been observed in carcinomas of the urinary bladder, lung, thymus, colon, pancreas, ovary, breast, kidney, and in melanoma and glioblastoma.
PD-L1 is a coinhibitory checkpoint molecule known for its role in dampening T-cell responses. However, previous clinical trials found that PD-L1 antibody treatment in patients whose tumor cells do not express PD-L1 can still be effective in inducing tumor regression, suggesting a tumor-independent effect of the treatment (16, 17). Treatment of tumor-bearing mice with PD-L1 antibody decreases tumor growth in mice deficient in T cells, which points to a lymphocyte-independent mechanism of action (42). This phenomenon was attributed to direct effects of PD-L1 antibodies on tumor cell growth through alterations in mTOR pathway signaling. Thus, there is precedent for antitumor effects induced by PD-L1 antibody treatment that may not be related to T-cell PD-1 expression. Several reports have suggested additional roles for PD-L1 in regulating tumor cell and dendritic cell activity (6-14), but little is known concerning the role of PD-L1 in regulating macrophage function.. Key findings from the studies ...
The disclosure provides methods for treating lung cancer (e.g., non-small cell lung cancer) with an anti-PD-L1 antibody in a patient identified using a polynucleotide or polypeptide marker of the disclosure: CXCL9, KRT8, TRIM29, and/or IFNgamma.
Programmed death ligand (PD-L) 1 is expressed on many tumors and inhibits anti-tumor T cells through programmed death (PD)-1. Tumor PD-L1 predicts αPD-L1 treatment effects, but mechanism(s) for PD-L1- tumor response to αPD-L1 are unclear. Our studies suggest tumor-intrinsic PD-L1 signals and spatially varied PD-L1 expression may contribute to response deviation. We used PD-L1+ B16 melanoma (ctrl) and made PD-L1KO by CRISPR. αPD-L1 slowed ctrl but not PD-L1KO B16 growth in mice as expected, but PD-L1KO also responded to αPD-L1 if ctrl B16 was on the trans flank. αPD-L1 elicited similar CD3+ T cell infiltration into ctrl vs. PD-L1KO tumors, but without detectable B16-specific T cell increase. CD11b+ cell infiltration was similar in ctrl and PD-L1KO. Strikingly, NKp46+ and NK1.1+ natural killer (NK) cells infiltrated PD-L1KO , ctrl. NK cells increased significantly (~2-fold) after αPD-L1 in PD-L1KO vs. ctrl, along with NK effector functions (e.g., IFN-γ). Tumor PD-L1 altered tumor chemokines ...
Durvalumab (MEDI 4736), developed by MedImmune (a subsidiary of AstraZeneca), is a fully human monoclonal antibody directed against programmed death ligand-1
INTRODUCTION: Green space in the built environment is an important topic on the health agenda today. Studies have shown that access to green spaces is associated with better mental and physical health, yet green spaces can also be detrimental to health if they are not managed appropriately. Despite the increasing interest in urban green spaces, little research has so far been conducted into the links between green spaces and cancer. OBJECTIVE: The purpose of this scoping review is therefore to map the literature available on the types of relationship between urban green spaces and cancer ...
Programmed death-ligand 1 (PD-L1) also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1) is a protein that in humans is encoded by the CD274 gene. The formation of PD-1 receptor / PD-L1 or B7.1 receptor /PD-L1 ligand complex transmits an inhibitory signal which reduces the proliferation of these CD8+ T cells at the lymph nodes. Supplementary to that PD-1 is also able to control the accumulation of foreign antigen specific T cells in the lymph nodes through apoptosis which is further mediated by a lower regulation of the gene Bcl-2.
It is now understood that PD-L1 protein expression is not binary; it is a continuous variable whereby a range of PD-L1 expression levels are observed, with tumor heterogeneity also frequently noted (21, 23, 31), all of which may have biological and/or clinical significance. Staining cutoffs are used to classify patients with high or low/no tumor PD-L1 expression (20, 23), and the cutoff appropriate for clinical decision making for each PD-1 or PD-L1 therapy is determined by clinical data.. Expression cutoffs for PD-L1 used in clinical trials to date vary between 1% and 50%, depending on the study and assay used (refs. 5, 7, 17, 19; Supplementary Table S1). Two recent reviews have examined the correlation between PD-L1 expression and outcome in patients with NSCLC treated with anti-PD-1 or anti-PD-L1 therapeutic agents (32, 33). One of these, a meta-analysis by Abdel-Rahman, found that the advantage of anti-PD-1 agents over docetaxel in second-line treatment of NSCLC is limited to tumors with ,1% ...
Expression of the immunosuppressive ligand PD-L1, detected in pretreatment tumor biopsies with IHC, has been associated with favorable clinical outcomes following PD-1- and PD-L1-blocking therapies in some studies in several types of cancer (1, 7, 9, 21). This can be understood by viewing PD-L1 as a surrogate marker for an immune-reactive TME, as inflammatory cytokines such as IFNγ are major drivers of PD-L1 expression on tumor and stromal cells. In this model, blocking the PD-1/PD-L1 interaction unleashes an immune response that is already properly trained and poised to attack cancer cells, but held in check by this immunosuppressive pathway. Despite the therapeutic impact of PD-1 blockade in many patients with certain cancer types (22), the majority of patients with PD-L1+ tumors do not respond to anti-PD-1/PD-L1 drugs, suggesting the involvement of additional factors in the TME contributing to treatment resistance. The current study attempts to identify such factors by exploring the gene ...
Programmed cell death 1 ligand 1 is one of the two ligands of PD-1. PD-L1 is expressed on macrophages, T cells, B cells, NK cells, DCs and some cancer cell surface. Binding of PD-1 with PD-L1 could result in down-regulation of the immune system by inhibiting the T-cell activation process. Thus, P...
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Merck, Pfizer and Verastem announced today that they have entered into an agreement to evaluate avelumab*, an investigational fully human anti-PD-L1 I
Learn more about FAZ053 (anti-PD-L1), an investigational immuno-oncology treatment being developed by Novartis for patients with advanced cancers.
Dr Ascierto talks to ecancertv at ITOC-3 about PD-L1 checkpoint inhibition. In particular, he discusses whether or not it can be truly considered a
Cell Phone Sally is helping people become more cell-phone savvy. Sponsored by the Commission on State Emergency Communications, the character is part of an education campaign to inform the public about the proper use of 9-1-1 . Cell Phone Sallys message will encourage people to verify their cellular phone number, as well as to identify landmarks when making a cellular 9-1-1 call, in order to ensure that emergency response arrives at the correct location. Children in particular need to become better acquainted with what to say, how to call, and when to call 9-1-1 for help. For more information on Cell Phone Sally or for any questions regarding this blog, please contact Melinda Crockom at [email protected] ...
Characterization of programmed cell death-1 ligand (PD-L1) expression in circulating tumor cells (CTCs) of lung cancer.2019-05-25T08:02:17-08:00 Characterization of programmed cell death-1 ligand (PD-L1) expression in circulating tumor cells (CTCs) of lung cancer.. ...
Programmed death-ligand 1 (PD-L1) also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1) is a protein that in humans is encoded by the CD274 gene. Programmed death-ligand 1 (PD-L1) is a 40kDa type 1 transmembrane protein that has been speculated to play a major role in suppressing the immune system during particular events such as pregnancy, tissue allografts, autoimmune disease and other disease states such as hepatitis. Normally the immune system reacts to foreign antigens that are associated with exogenous or endogenous Danger signals, which triggers a proliferation of antigen-specific CD8+ T cells and/or CD4+ helper cells. The binding of PD-L1 to PD-1 or B7.1 transmits an inhibitory signal that reduces the proliferation of these T cells and can also induce apoptosis, which is further mediated by a lower regulation of the gene Bcl-2. PD-L1 was characterized at the Mayo Clinic as an immune regulatory molecule, B7-H1. Later this molecule was renamed as PD-L1 because it was ...
CD273 / PD-L2 (programmed death ligand-1), also known as B7-DC, is a member of the B7 family of regulatory proteins. It costimulates the proliferation of T cells, and mediates IFN gamma production. Ligation of CD273 on dendritic cells enhances dendritic cell activation and T cell responses. When interacting with CD279, it can act as a coinhibitor of the T cell function. CD273 expression is a useful marker to distinguish primary mediastinal B cell lymphoma from other diffuse large B cell lymphomas ...
The results of this study show that the PD-1 pathway is important in the alleviation of chronic GVHD. Blockade of the PD-1 pathway using anti-PD-1, anti-PD-L1, or anti-PD-L2 mAbs exacerbated chronic GVHD, and chimeric mice showed the importance of PD-L1 expression in host tissues in attenuating chronic GVHD. BMT into PD-L1-deficient recipients revealed IL-17+IFN-γ+ T cell expansion and Am80 administration of Am80 overcame the IL-17+IFN-γ+ T cell expansion caused by PD-L1 deficiency, resulting in reduced chronic GVHD damage in PD-L1−/− recipients. Stimulation of the PD-1 pathway with an agonistic anti-PD-1 mAb alleviated chronic GVHD, suggesting a new target for the prevention or treatment of chronic GVHD.. T cell activation via the TCR and costimulatory molecules has been well characterized, whereas coinhibitory pathways, which regulate T cell tolerance, are also known (32). The PD-1R and its ligands were identified and their inhibitory roles have become better understood (5-7, 9, 20, 21, ...
In a very important recent study, Chen and colleagues describe that PD-L1 (B7-H1, CD274) is expressed on both malignant cells and infiltrating macrophages in a subset of aggressive B-cell lymphomas (1). The article highlights the possibilities of targeting the PD-1/PD-L1 pathway in these malignancies. Interactions between PD-1 on T cells and the ligand PD-L1 (B7-H1) control the induction and maintenance of peripheral T-cell tolerance during normal immune responses. Accordingly, tumor-infiltrating lymphocytes are inhibited by PD-L1 at the tumor site because of elevated levels of PD-1 on the surface of such T cells. Indeed, blockade of either PD-1 or PD-L1 resulted in objective clinical responses (2). Remarkably, an association between objective clinical response and PD-L1 expression on tumor cells was described (2). Taube and colleagues furthermore recently described that T cells may actually trigger their own inhibition by secreting cytokines that drive tumor PD-L1 expression (3). However, the ...
Tumors can be recognized by the immune system, but they have multiple mechanisms for evading eradication by the immune system. The tumor microenvironment suppresses the immune response, partly because tumors can express molecules that inhibit immune responses. The cancer clinical trials summarized by Dr. Herbst and Dr. Wolchok use a new strategy that blocks major pathways the tumor uses to suppress the immune response.. Underlying Mechanisms. Immunoinhibitory receptors regulate T-cell activation, tolerance, and "exhaustion." T-cell exhaustion is a dysfunctional state that develops in the setting of chronic antigen stimulation (such as occurs in a chronic infection or tumor). Immune responses against tumors are an ongoing chronic fight. Multiple inhibitory receptors contribute to T-cell exhaustion, and these are targets for immunotherapy. Tumor infiltrating lymphocytes can express many immunoinhibitory receptors, and these are druggable targets for immunotherapy. This inhibitory strategy is often ...
Anti-PD-L1 antibodies constitute the second class of therapeutics targeting the PD-1 pathway...PD-L1 is also important in...predicting response to therapy...the utility of this marker...was subject of considerable discussion. When ORR is 40% it is helpful to select patients prospectively. In a study of responsiveness to pembro, Kefford, used an analysis of PD-L1 expression to demonstrate a remarkable difference in...response between patients with greater or = 1% PD-L1 expression vs patients who were PD-L1 negative. Biopsy 2 months before pembro determined PD-L1 expression. Patients were given Pembro at either 10mg/kg q2wk, 10mg/kg q3wk, or 2mg/kg q 3 wk with median treatment of 23 weeks and 13 month follow-up. ORR = 41%. Median PFS = 31 weeks and median OS was not reached. 1 year survival = 81%. So this was a terrific cohort within the larger pembro study, likely due to the higher dose used. PD-L1 expression was associated with improved ORR by 51% vs 6%, PFS = median 12 vs 3 months, and 1 year ...
Immunosenescence is the age-associated dysregulation of the immune system, of high clinical relevance, as it contributes to multiple age-related comorbidities, including malignancies, infectious diseases, autoimmune diseases, and degenerative diseases. T cells are important components of the immune system. Age-associated T-cell dysfunction is important for the development of immunosenescence. T-cell senescence is different from T-cell exhaustion, a hyporesponsiveness associated with chronic infections and cancer. Exhausted T cells are derived from activated T cells that progressively lose function because of persistent antigen stimulation, whereas senescence is cell cycle arrest due to aging. However, emerging evidence indicates that T-cell senescence shares several key features with exhaustion. The upregulation of multiple co-inhibitory receptors is not only a hallmark, but also an important mechanism involved in the development of T-cell exhaustion. Consistently, certain co-inhibitory ...
Immune rejection of tumors is mediated by IFN-γ production and T cell cytolytic activity. These processes are impeded by PD-1, a co-inhibitory molecule expressed on T cells that is elevated in tumor-infiltrating lymphocytes (TIL). PD-1 elevation may reflect T cell exhaustion marked by decreased proliferation, production of type 1 cytokines and poor cytolytic activity. Although anti-PD-1 antibodies enhance IFN-γ secretion after stimulation of the T cell receptor (TCR), the mechanistic link between PD-1 and its effects on T cell help (Tc1/Th1 skewing) remains unclear. In prospectively collected cancer tissues, we found that TIL exhibited dampened Tc1/Th1 skewing and activation compared to peripheral blood lymphocytes (PBL). When PD-1 bound its ligand PD-L1 we observed a marked suppression of critical TCR target genes and Th1 cytokines. Conversely, PD-1 blockade reversed these suppressive effects of PD-1: PD-L1 ligation. We also found that the TCR regulated phosphatase SHP-2 was expressed more ...
Because the bona fide memory cells in the Ly6C+ PD-1− population may have biased the results by being the major contributors to cytokine production, we also compared the production of IFNγ and TNFα in the Ly6C− population, separated into PD-1+ or PD-1− cells. Only 10 ± 1.1% (n = 4) of PD-1+Ly6C− cells produced IFNγ after anti-CD3 stimulation, in contrast to 37 ± 1.8% (n = 4) of the PD-1−Ly6C− cells (not depicted). Similarly, only 4.1 ± 2.5% (n = 3) of the PD-1+Ly6C− cells produced TNFα, in contrast to 40 ± 7.2% (n = 3) of the PD-1−Ly6C− cells. The abilities of these three fractions to synthesize IFNγ or TNFα after anti-CD3 stimulation are summarized in Table I.. We next tested whether the expression of PD-1 may be a cause of the T cell dysfunction by incorporating 25 μg/ml anti-PD-L1 mAb into cultures of day 14 HP cells for 3 d. The frequencies of PD-1+ cells producing IFNγ were significantly enhanced in the presence of anti-PD-L1 mAb (No antibody treatment, 6.6 ± ...
TY - JOUR. T1 - Differential expression of immune-regulatory genes associated with PD-L1 display in melanoma. T2 - Implications for PD-1 pathway blockade. AU - Taube, Janis M. AU - Young, Geoffrey D.. AU - McMiller, Tracee L.. AU - Chen, Shuming. AU - Salas, January T.. AU - Pritchard, Theresa S.. AU - Xu, Haiying. AU - Meeker, Alan Keith. AU - Fan, Jinshui. AU - Cheadle, Chris. AU - Berger, Alan E.. AU - Pardoll, Andrew Mark. AU - Topalian, Suzanne. PY - 2015/9/1. Y1 - 2015/9/1. N2 - Purpose: Blocking the immunosuppressive PD-1/PD-L1 pathway has antitumor activity in multiple cancer types, and PD-L1 expression on tumor cells and infiltrating myeloid cells correlates with the likelihood of response. We previously found that IFNG (interferon-gamma) was overexpressed by tumor-infiltrating lymphocytes in PD-L1+ versus PD-L1(-) melanomas, creating adaptive immune resistance by promoting PD-L1 display. This study was undertaken to identify additional factors in the PD-L1+ melanoma microenvironment ...
Recent studies in cancer research have focused intensely on the antineoplastic effects of immune checkpoint inhibitors. While the development of these inhibitors has progressed successfully, strategies to further improve their efficacy and reduce their toxicity are still needed. We hypothesized that the delivery of anti-PD-1 antibody encapsulated in PLGA nanoparticles (anti-PD-1 NPs) to the spleen would improve the antitumor effect of this agent. Unexpectedly, we found that mice treated with a high dose of anti-PD-1 NPs exhibited significantly higher mortality compared with those treated with free anti-PD-1 antibody, due to the overactivation of T cells. Administration of anti-PD-1 NPs to splenectomized LT-α-/- mice, which lack both lymph nodes and spleen, resulted in a complete reversal of this increased mortality and revealed the importance of secondary lymphoid tissues in mediating anti-PD-1-associated toxicity. Attenuation of the anti-PD-1 NPs dosage prevented toxicity and significantly ...
Programmed death-ligand 1 (PD-L1) testing serves as a diagnostic approach for stratifying patients with nonsmall cell lung cancer (NSCLC) and tailoring treatment. PD-L1 expression has been observed either on tumor cells or on tumor-infiltrating immune cells, but the mechanistic implications of this expression are unclear. To investigate PD-L1 expression in tumor cells and immune cells, Marcin Kowanetz et al. (pp. E10119-E10126) retrospectively characterized tumor specimens from 4,549 patients with NSCLC for PD-L1 expression. The authors found that NSCLC tumors with PD-L1 expression on tumor cells had different histological and molecular characteristics from those with PD-L1 expression on immune cells, with high PD-L1 expression on tumor cells associated with poor immune infiltration. PD-L1 expression on immune cells, with or without associated expression on tumor cells, was more prevalent and thought to reflect interferon-gamma-induced adaptive regulation. In contrast, PD-L1 expression solely on ...
Lenalidomide will be administered orally (PO) until loss of clinical benefit, withdrawal, or study end. Cohort B1 will receive 10, 15, or 25 mg, ascending-dose lenalidomide, on Days 1-14 of each 21-day cycle. Cohort C will receive 10 mg on Days 1-14 of each 21-day cycle, beginning in Cycle 4. Cohort E (combination with daratumumab) will receive 10, 15, or 25 mg on Days 1-21 of each 28-day cycle. Participants in Cohort E1 will receive ascending-dose lenalidomide, and those in Cohort E2 will receive lenalidomide at the MTD as determined in Cohort E1 ...
Have not received prior systemic therapy treatment for their advanced/Stage four NSCLC. Completion of treatment with cytotoxic chemotherapy, biological therapy, and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic disease. Confirmation of resolution of toxic effects of previous neoadjuvant/adjuvant chemotherapy therapy to Grade less than or equal to 1. For radiation toxicity or prior major surgeries, participants should have recovered from side effects and/or ...
Glycosylation of immune receptors and ligands, such as T cell receptor and coinhibitory molecules, regulates immune signaling activation and immune surveillance. However, how oncogenic signaling initiates glycosylation of coinhibitory molecules to induce immunosuppression remains unclear. Here we show that IL-6-activated JAK1 phosphorylates programmed death-ligand 1 (PD-L1) Tyr112, which recruits the endoplasmic reticulum-associated N-glycosyltransferase STT3A to catalyze PD-L1 glycosylation and maintain PD-L1 stability. Targeting of IL-6 by IL-6 antibody induced synergistic T cell killing effects when combined with anti-T cell immunoglobulin mucin-3 (anti-Tim-3) therapy in animal models. A positive correlation between IL-6 and PD-L1 expression was also observed in hepatocellular carcinoma patient tumor tissues. These results identify a mechanism regulating PD-L1 glycosylation initiation and suggest the combination of anti-IL-6 and anti-Tim-3 as an effective marker-guided therapeutic ...
Inhibitors of PD-1 signaling have revolutionized cancer therapy. PD-1 and PD-L1 antibodies have been approved for the treatment of cancer. To date, therapeutic PD-1 inhibitors have not been compared in a functional assay. We used an efficient T cell reporter platform to evaluate the efficacy of five clinically used PD-1 inhibitors to block PD-1 signaling. The half maximal effective concentrations (EC50) for nivolumab and pembrolizumab were 76.17 ng/ml (95% CI 64.95-89.34 ng/ml) and 39.90 ng/ml (34.01-46.80 ng/ml), respectively. The EC50 values of the PD-L1 inhibitors were 6.46 ng/ml (5.48-7.61 ng/ml), 6.15 ng/ml (5.24-7.21 ng/ml) and 7.64 ng/ml (6.52-8.96 ng/ml) for atezolizumab, avelumab, and durvalumab, respectively. In conclusion, a functional assay evaluating antibodies targeting PD-1 inhibition in vitro revealed that pembrolizumab is a slightly more effective PD-1 blocker than nivolumab, and that PD-L1 antibodies are superior to PD-1 antibodies in reverting PD-1 signaling.
CancerConnect News: The checkpoint inhibitor Keytruda (pembrolizumab) has been reported to produce an overall response rate of 30% in patients with PD-L1-positive, advanced esophageal cancer.1. About Keytruda. Keytruda is a monoclonal antibody that helps to restore the bodys immune system in fighting cancer. It creates its anti-cancer effects by blocking a specific protein used by cancer cells called the programmed death-ligand 1 (PD-L1), to escape an attack by the immune system. Once PD-L1 is blocked, cells of the immune system are able to identify cancer cells as a threat, and initiate an attack to destroy the cancer.. About Esophageal Cancer. The esophagus is a muscular tube that food and liquids pass through on their on their way to the stomach. Each year in the United States, more than 17,000 people are diagnosed with cancer of the esophagus and more than 15,000 die of the disease.2 Although many people with esophageal cancer are diagnosed with advanced disease, treatment has slowly ...
This purpose of this study is to evaluate the safety and tolerability of study drug atezolizumab when administered with bevacizumab and FOLFOX in patients with gastric cancer. This study will also evaluate the safety and tolerability of atezolizumab administered with nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer.
When you express interest in a specific study, the information from your profile will be sent to the doctor conducting that study. If youre eligible to participate, you may be contacted by a nurse or study coordinator. If you select a health category rather than a specific study, doctors who have active studies in that area may contact you to ask if you would like to participate. In both cases, you will be contacted by the preferred method (email or phone) that you specified in your profile. ...
HiPath™ Supports Pathologists with Advanced Image Analysis of PD-L1 Assays CARLSBAD, CA, May 11, 2017 - Applied Spectral Imaging (ASI), a global leader of computer-assisted microscopy, introduces HiPath imaging and analysis of PD-L1 assays. PD-L1 is seen as the current breakthrough therapeutic target in immuno-oncology. Following recent clinical advances, PD-L1 expression has become a key factor in […]. ...
Merck, known as MSD outside the United States and Canada, announced that Keytruda (pembrolizumab), the companys anti-PD-1 therapy, has been approved in Japan for the treatment of certain patients with PD-L1-positive unresectable
Researchers tested the combined treatment in mice, after detecting increased PAK4 expression and reduced immune infiltration in melanoma patients with poor anti-PD-1 response.
Programmed cell death-1 (PD-1) is an immune inhibitory receptor that is expressed transiently on the surface of CD4 and CD8 T cells following immune activation...
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Programmed death ligand-1 (PD-L1) interacts with programmed death-1 (PD-1) and the immunostimulatory molecule CD80 and functions as a checkpoint to regulate immune responses. The interaction of PD-L1 with CD80 alone has been shown to exacerbate the severity of graft-versus-host disease (GVHD), whereas costimulation of CD80 and PD-1 ameliorates GVHD. Here we have demonstrated that temporary depletion of donor CD4+ T cells early after hematopoietic cell transplantation effectively prevents GVHD while preserving strong graft-versus-leukemia (GVL) effects in allogeneic and xenogeneic murine GVHD models. Depletion of donor CD4+ T cells increased serum IFN-γ but reduced IL-2 concentrations, leading to upregulation of PD-L1 expression by recipient tissues and donor CD8+ T cells. In GVHD target tissues, the interactions of PD-L1 with PD-1 on donor CD8+ T cells cause anergy, exhaustion, and apoptosis, thereby preventing GVHD. In lymphoid tissues, the interactions of PD-L1 with CD80 augment CD8+ T cell ...
The blockade of immune checkpoints, such as programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), is a promising novel approach in cancer treatment. As these pathways are non-redundant, dual targeting may have additive or synergistic antitumour activity. Durvalumab (MEDI4736) is a selective, high affinity human IgG1 mAb that blocks programmed cell death ligand-1 (PD-L1) binding to PD-1 (IC50 0.1 nM) and CD80 (IC50 0.04 nM), and tremelimumab is a selective human IgG2 mAb inhibitor of CTLA-4. In a Phase 1b study (NCT02000947), durvalumab + tremelimumab has shown encouraging clinical activity (objective response rate [ORR] 33% [95% CI 17-54%] across tremelimumab 1 mg/kg cohorts [n = 27]) and manageable tolerability in patients (pts) with both PD-L1-positive and -negative NSCLC. NEPTUNE is a Phase 3 study to determine the efficacy and safety of durvalumab + tremelimumab combination therapy versus standard of care (SoC) platinum-based doublets in the first-line ...
Programmed cell death-1 (PD-1) and its ligands, particularly PD-L1 and PD-L2, are the most important proteins responsible for signaling T-cell inhibition and arbitrating immune homeostasis and tolerance mechanisms. However, the adaptive evolution of these genes is poorly understood. In this study, we aligned protein-coding genes from vertebrate species to evaluate positive selection constraints and evolution in the PD1, PD-L1 and PD-L2 genes conserved across up to 166 vertebrate species, with an average of 55 species per gene. We determined that although the positive selection was obvious, an average of 5.3% of codons underwent positive selection in the three genes across vertebrate lineages, and increased positive selection pressure was detected in both the Ig-like domains and transmembrane domains of the proteins. Moreover, the PD1, PD-L1 and PD-L2 genes were highly expressed in almost all tissues of the selected species indicating a distinct expression pattern in different tissues among most species.
Blocking interaction of the immune checkpoint receptor PD-1 with its ligand PD-L1 is associated with good clinical outcomes in a broad variety of malignancies. High levels of PD-L1 promote tumour growth by restraining CD8+ T-cell responses against tumors. Limiting PD-L1 expression and function is therefore critical for allowing the development of anti-tumour immune responses and effective tumour clearance. PKM2 is also a key player in regulating cancer as well as immune responses. PKM2 catalyzes the final rate-limiting step of glycolysis. Furthermore PKM2 as a dimer translocates to the nucleus, where it stimulates Hif-1α transactivation domain function and recruitment of p300 to the Hif-1α response elements (HRE) of Hif-1α target genes. Here, we provide the first evidence of a role for PKM2 in regulating the expression of PD-L1 on macrophages, dendritic cells (DCs), T cells and tumour cells. LPS-induced expression of PD-L1 in primary macrophages was inhibited by the PKM2 targeting compound TEPP-46.
Due to the relative rarity, sub-optimal current treatment strategies, and commonly observed chemoresistance of NKTCL, it is urgently warranted to identify novel therapeutic targets. Blockade of PD-1/PD-L1 interactions has emerged as a promising immunotherapy for cancer patients [24-27]. Previous studies have revealed aberrant expressions of PD-1/PD-L1 in NKTCL cell lines and tissues as well as involvement of PD-1/PD-L1 in the downregulation of antitumor immunity, suggesting that PD-1/PD-L1 may serve as a potential candidate for immunotherapy in NKTCL [28]. In the present study, we focused on the interactions between EBV infection and PD-L1 expression in NKTCL cell lines, as well as the prognostic impact of PD-L1 expression in NKTCL patients. Our findings included the following: (1) PD-L1 expression positively correlated LMP1 expression at both protein and mRNA levels in NKTCL and NK cells; (2) PD-L1 expression was upregulated by LMP1 through the MAPK/NF-κB pathway; and (3) the levels of PD-L1 ...
Woessner, PhD, MS D. Woessner, PhD, MS D Woessner, PhD, MS, David.. "Programmed Cell Death-1 (PD-1) Pathway Checkpoint Inhibition: Immuno-oncology for Advanced Melanoma." Goodman & Gilmans The Pharma. Basis of Therapeutics Updates Brunton LL. Brunton L.L. Brunton, Laurence L. New York, NY: McGraw-Hill, 2016, http://accessanesthesiology.mhmedical.com/updatesContent.aspx?gbosid=195057§ionid=75622512. ...
Programmed cell death ligand 1 (PD-L1) is an important immune-inhibitory protein expressed on cancer cells to mediate cancer escape through interaction with PD-1 expressed on activated T lymphocytes (T cells). Previously, we reported that colon and breast cancer stem cells (CSCs) expressed much higher levels of PD-L1 than their parental cells, suggesting they will be more resistant to immune attack. We investigated the underlining mechanism of PD-L1 increase in colon CSCs, with a special focus on the effect of insulin and epithelial growth factor (EGF), the two fundamental components to sustain the metabolism and stemness in the culture of CSCs. We found that insulin increased the total and surface PD-L1 levels through PI3K/Akt/mTOR pathway as the increase could be inhibited by the dual inhibitor of the pathway, BEZ235. EGF didnt affect the total PD-L1 levels of CSCs but increased the cell surface protein levels by flow cytometry analysis, indicating EGF promotes the transport of PD-L1 to the cell
The programmed cell death protein 1 (PD-1) is expressed by activated T cells that act as an immunoregulatory molecule, and are responsible for the negative regulation of T cell activation and peripheral tolerance. The PD-1 gene also encodes an inhibitory cell surface receptor involved in the regulation of T cell functions during immune responses/tolerance. Beyond potent inhibitory effects on T cells, PD-1 also has a role in regulating B cell and monocyte responses. An overexpression of PD-1 has been reported to contribute to immune system avoidance in different cancers. In particular, PD-1 over-expression influences tumor-specific T cell immunity in a cancer microenvironment. Blocking the PD-1/PD-1 ligand (PD-L1) pathway could potentially augment endogenous antitumor responses. Along these lines, the use of PD-1/PD-L1 inhibitors has been applied in clinical trials against diverse forms of cancer. It was believed that antibodies targeting PD-1/PD-L1 might synergize with other treatments that ...
Immune check points are a topic of increasing interest in the field of cancer immunology, as molecular research has begun to explain the complex mechanisms regulating cellular immune responses [3]. For example, there are a number of inhibitory mechanisms that can be induced by the activated immune system, especially in T-cells, which can prevent an excessive immune response [4-6]. Programmed death-1 (PD-1) was initially cloned in 1992 during a study of thymus T-cell molecules [7], and a study from 2000 revealed that one PD-1 ligand (programmed death ligand 1 [PD-L1], B7-H1, and CD274) induces T-cell apoptosis. These discoveries led to research regarding the function of PD-1 as an immune checkpoint [8], which revealed that PD-1 is only expressed in activated T-cells, and that PD-1 and CD28 regulate their response through ligand binding. The ligands of PD-1 are PD-L1 and PD-L2 (B7-DC, CD273), with PD-L1 being expressed on many cell types (e.g., immune cells, epithelial cells, and endothelial ...
Head and neck cancer (HNC) patients often present with advanced metastatic disease. Whilst there have been improvements in the management of locoregional disease, distant metastatic spread remains a challenge in the field [1-3]. Palliative chemotherapy is platinum based and for patients who progress after first line treatment or are refractory, therapeutic options are limited. Numerous agents including cetuximab, paclitaxel, gemcitabine and docetaxel have been assessed prospectively in the treatment of platinum refractory patients and the time to progression ranged from 2 to 6 months [4]. These systemic treatments produce a significant degree of morbidity and new therapeutic options are therefore a need in these patients. Once there is an established role in metastatic disease, translation into the curative setting is appropriate.. The programmed cell death-1/programmed cell death-1 ligand (PD-1/PD-L1) pathway has shown to play a crucial role in tumour immune invasion. Recent literature suggests ...
Immunotherapy with anti-programmed death-1 (PD-1) or anti-PD-1 ligand 1 (PD-L1) antibodies has been approved for the treatment of several cancers because of impressive durable responses; however, overall, only a small percentage of patients currently benefit from PD-1 blockade therapy alone (Topalian et al., 2012; Herbst et al., 2014; Powles et al., 2014; Ansell et al., 2015; Garon et al., 2015; Postow et al., 2015; Robert et al., 2015a,b; Weber et al., 2015; Nghiem et al., 2016; Ribas et al., 2016). The combination of anti-PD-1/L1 antibodies with other immune modulating agents seems to be more active, but it adds significant toxicities (Wolchok et al., 2013; Larkin et al., 2015; Postow et al., 2015), which may be unwarranted for patients who would respond to anti-PD-1/L1 alone or for patients whose tumors would not respond anyway to either approach. Toxicities of combined immunotherapies may be lower using different agents or with sequential therapy (Weber et al., 2016), but it would still be ...
Efficacious antitumor vaccines strongly stimulate cancer-specific effector T cells and counteract the activity of tumor-infiltrating immunosuppressive cells. We hypothesised that combining cytokine expression with silencing programmed cell death ligand 1 (PD-L1) could potentiate anticancer immune responses of lentivector vaccines. Thus, we engineered a collection of lentivectors that simultaneously co-expressed an antigen, a PD-L1-silencing shRNA, and various T cell-polarising cytokines, including interferon γ (IFNγ), transforming growth factor β (TGFβ) or interleukins (IL12, IL15, IL23, IL17A, IL6, IL10, IL4). In a syngeneic B16F0 melanoma model and using tyrosinase related protein 1 (TRP1) as a vaccine antigen, we found that simultaneous delivery of IL12 and a PD-L1-silencing shRNA was the only combination that exhibited therapeutically relevant anti-melanoma activities. Mechanistically, we found that delivery of the PD-L1 silencing construct boosted T cell numbers, inhibited in vivo tumor growth
While anti-PD-1 antibodies have been a breakthrough in the treatment of patients with advanced melanoma, a substantial proportion of patients are still refracto...
Richard W. Joseph, MD, notes that current treatment guidelines for melanoma recommend anti-PD-1 agents as front line therapy and discusses payer coverage for first-line use of these agents.
-Increasing Activated T Cells in Tumors Demonstrates Potential Complement to anti-PD-1 and anti-PD-L1 Checkpoint Inhibitors-. TUSTIN, Calif., Aug. 26, 2015-- Peregrine Pharmaceuticals, Inc., a biopharmaceutical company focused on developing therapeutics to stimulate the bodys immune system to fight cancer, today announced the presentation of a range of...
From BioPortfolio: By connecting highly effective cancer immunotherapy drugs such as anti-CTLA4 (ipilimumab) and anti-PD-L1 (atezolizumab) to peptides that bind to tissues in and ...
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HiPath™ Supports Pathologists with Advanced Image Analysis of PD-L1 Assays CARLSBAD, CA, May 11, 2017 - Applied Spectral Imaging (ASI), a global leader of computer-assisted microscopy, introduces HiPath imaging and analysis of PD-L1 assays. PD-L1 is seen as the current breakthrough therapeutic target in immuno-oncology. Following recent clinical advances, PD-L1 expression has become a key factor in […]. ...
Ovarian cancer remains the most lethal gynaecological cancer mainly due to the lack of reliable biomarkers and eventual development of chemo-resistance. This emphasizes the need for better therapies. Ovarian cancer is considered as an immunogenic tumour and adoptive immunotherapy is a promising treatment strategy. However, co-inhibitory molecules such as programmed death-ligand 1 (PD-L1), highly expressed on ovarian cancer cells interacts with its receptor, programmed death-1 (PD-1), expressed on T cells, causing immunosuppression. The aim of this Ph.D. was to 1) develop more efficient and targeted gene delivery agents by functionalizing poly(ethylenimine) (PEI) with various hydrophobic groups and folic acid (FA) targeting ligand, 2) deliver PD-L1 small interfering RNA (siRNA) or short hairpin RNA (shRNA) into ovarian cancer cells to block PD-1/PD-L1 interactions and 3) to study how T cell function and anti-tumour activity are affected as a consequence of PD-L1 knockdown. 4) In addition, ...
Programmed cell death protein 1/programmed cell death protein ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte antigen 4/B7 (CTLA-4/B7) pathways are key regulators in T-cell activation and tolerance. Nivolumab, pembrolizumab (PD-1 inhibitors), atezolizumab (PD-L1 inhibitor) and ipilimumab (CTLA-4 inhibitor) are monoclonal antibodies approved for treatment of several advanced cancers. Immune checkpoint inhibitors (ICIs)-related hypophysitis is described more frequently in patients treated with anti-CTLA-4; however, recent studies reported an increasing prevalence of anti-PD-1/PD-L1-induced hypophysitis which also exhibits slightly different clinical features. We report our experience on hypophysitis induced by anti-PD-1/anti-PD-L1 treatment. We present four cases, diagnosed in the past 12 months, of hypophysitis occurring in two patients receiving anti-PD-1, in one patient receiving anti-PD-1 and anti-CTLA-4 combined therapy and in one patient receiving anti-PD-L1. In this case series, timing, ...
Costimulatory molecules, such as B7-1/2 and PD-L1/2 play an important role in the function of APC. The regulation of the surface levels of costimulatory molecules is one mechanism by which APC maintain the balance between tolerance and immunity. We examined the contributions of B7-1/2 and PD-L1/2 to the function of IL-10-treated, immunosuppressive DC as well as therapeutic exosomes derived from these DC. IL-10 treatment of DC significantly downregulated surface expression of MHC II, B7-1, B7-2, and decreased levels of MHC I and PD-L2. IL-10 treatment of DC resulted in a modified costimulatory profile of DC-secreted exosomes with a reduction in B7-1, PD-L1 and PD-L2. We further demonstrate that absence of B7-1 or B7-2 on donor DC results in a loss of ability of IL-10-treated DC and their exosomes to suppress the delayed-type hypersensitivity response, whereas IL-10-treated DC deficient in PD-L1/2 as well as their secreted exosomes retained the ability to suppress delayed-type hypersensitivity ...
PD-L1 immunohistochemistry (IHC) on tumor tissue is an important predictive biomarker for anti-PD-1/anti-PD-L1 cancer immunotherapy. PD-L1 IHC is a companion diagnostic for the utilization of anti-PD-1 directed therapies in non-small cell lung cancer (NSCLC) and bladder cancer, and can predict response to immune checkpoint blockade. However, tissue biopsy is not always available or may be insufficient to accurately test for PD-L1 expression and biopsy samples may not reflect the actual PD-L1 expression of the tumor due to tumor heterogeneity. Given this heterogeneity and the risks inherent with tissue biopsy, the ability to detect tumor PD-L1 status with a simple blood draw would be a major advance in this field. In addition to minimizing patient risk from a tissue biopsy, a circulating biomarker assay can avoid biopsy selection bias and provide a snapshot of the dynamic tumor landscape ...
Two vaccines expressing Compact disc4+ and Compact disc8+ Testosterone levels cell epitopes of MAAs by a chimpanzee-derived replication-defective AdC68 vector were compared in a mouse model of most cancers. in existence of gD are much less vulnerable to tumor-driven fatigue. Intro Actually tumor vaccines that are extremely immunogenic in pet versions frequently fail to offer benefits to individuals with advanced malignancies (1, 2). This offers partly been connected to the extremely immunosuppressive growth microenvironment, which states immunoinhibitory ligands (3), employees suppressive cell subsets such as regulatory Capital t cells (4) and myeloid suppressor cells (5) and provides a metabolically pressured milieu (6). Biologicals that stop immunoinhibitory paths such as antibodies to PD-1 (7, 8) or CTLA-4 (9) Amyloid b-peptide (42-1) (human) manufacture or both (10, 11) are becoming examined only or in mixture with energetic immunotherapy in tumor individuals and possess produced ...
The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to Genentechs investigational cancer immunotherapy MPDL3280A for the treatment of PD-L1-positive non-small cell lung cancer (NSCLC) that has progressed during or after platinum-based chemotherapy (and an appropriate targeted therapy for those with an EGFR mutation-positive or ALK-positive tumor).. MPDL3280A (also known as anti-PD-L1) is an investigational monoclonal antibody designed to interfere with a protein called programmed death ligand 1 (PD-L1). MPDL3280A is designed to target PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, preventing it from binding to PD-1 and B7.1 on the surface of T cells. By inhibiting PD-L1, MPDL3280A may enable the activation of T cells, restoring their ability to effectively detect and attack tumor cells.. This Breakthrough Therapy designation is based on early results of MPDL3280A in patients whose NSCLC was characterized as PD-L1-positive by an ...
Darmstadt, Germany (ots/PRNewswire) - - First patient begins treatment in an international Phase II study investigating the efficacy and safety of MSB0010718C in patients with...
Tumor cell-surface expression of PD-L1 was drastically correlated with an objective scientific reaction (graph in the remaining). No patients with PD-L1-unfavorable tumors experienced an goal reaction. From the 25 people with PD-L1-optimistic tumors, two who were classified as not obtaining experienced a response at time of data Investigation remain less than evaluation. Proven at the ideal are immunohistochemical Assessment With all the anti-PD-L1 monoclonal antibody 5H1 in the specimen of the lymph-node metastasis from a individual with melanoma (leading), a nephrectomy specimen from a individual with renal-cell cancer (RCC) (Center), in addition to a specimen of a Mind metastasis from the affected person with lung adenocarcinoma (base). The arrow in Each and every specimen implies a person of many tumor cells with surface area-membrane staining for PD-L1. The asterisk signifies a normal glomerulus while in the nephrectomy specimen, which was adverse for PD-L1 staining ...
Tumor cell-area expression of PD-L1 was drastically correlated with the objective clinical reaction (graph with the left). No patients with PD-L1-negative tumors had an objective reaction. Of the twenty five sufferers with PD-L1-optimistic tumors, 2 who were classified as not getting experienced a response at enough time of information Investigation remain below analysis. Demonstrated at the ideal are immunohistochemical Assessment Along with the anti-PD-L1 monoclonal antibody 5H1 in a specimen of the lymph-node metastasis from a client with melanoma (top), a nephrectomy specimen from a individual with renal-cell most cancers (RCC) (Center), as well as a specimen of the brain metastasis from the patient with lung adenocarcinoma (bottom). The arrow in each specimen signifies 1 of numerous tumor cells with area-membrane staining for PD-L1. The asterisk suggests a normal glomerulus while in the nephrectomy specimen, which was adverse for PD-L1 staining ...
Inactivation of MYC induces tumor regression through both cell-autonomous mechanisms, including proliferative arrest and induction of apoptosis, and host-dependent mechanisms, such as inhibition of tumor angiogenesis and induction of tumor cell senescence (1-4, 13). We investigated the effect of enforced expression of CD47 or PD-L1 on these mechanisms and found that CD47 or PD-L1 expression prevented the shutdown of angiogenesis after MYC inactivation, as measured by the presence of CD31+ microvessels (Fig. 4E and fig. S15A) and expression of Ang2 and Tie2 (fig. S15C). The induction of tumor cell senescence, as measured by β-galactosidase (Fig. 4F and fig. S15B) and p15Ink4b and p19ARF levels (fig. S15D), was also affected, but we did not observe any effect on apoptosis or proliferation, as evaluated by annexin V and 7-AAD (fig. S16A), cleaved caspase 3 (fig. S16, B and D), and phospho-histone H3 (fig. S16, C and E). Therefore, the down-regulation of CD47 and PD-L1 appears to be required for ...
The association of PD-L1 expression with the efficacy of anti- PD-1/PD-L1 immunotherapy and survival of non-small cell lung cancer patients: a meta-analysis of randomized controlled trials
However, many patients are primarily resistant to immune checkpoint blockade -based monotherapy and many others will eventually relapse. As we start utilizing more of immunotherapeutic agents as standard of care and part of clinical trials, we need to think about potential resistance and developing novel combinations. Besides the B7 co-inhibitory receptors, OX40 (CD134), 4-1 BB (CD137) are co-stimulatory molecule can be expressed by activated immune cells and trials are ongoing with drugs targeting these alone or in combination with checkpoint inhibitors. In addition, there are novel intratumoral agents like TLR7/8 agonists, which are being tested in trials ...
Loss-of-function mutations in genes encoding TET DNA dioxygenase occur frequently in hematopoietic malignancy, but rarely in solid tumors which instead commonly have reduced activity. The impact of decreased TET activity in solid tumors is not known. Here we show that TET2 mediates interferon γ (IFNγ)-JAK-STAT signaling pathway to control chemokine and PD-L1 expression, lymphocyte infiltration and cancer immunity. IFNγ stimulated STAT1 to bind TET2 and recruit TET2 to hydroxymethylate chemokine and PD-L1 genes. Reduced TET activity was associated with decreased TH1-type chemokines and tumor-infiltrating lymphocytes (TILs) and the progression of human colon cancer. Deletion of Tet2 in murine melanoma and colon tumor cells reduced chemokine expression and TILs, enabling tumors to evade anti-tumor immunity and to resist anti-PD-L1 therapy. Conversely, stimulating TET activity by systematic injection of its co-factor, ascorbate/vitamin C, increased chemokine and TILs, leading to enhanced ...
Exclusions: Patients with active untreated unstable CNS metastases that require treatment - see trial for details; Patient must not have received more than two prior lines incorporating anti-PD-1, anti-PD-L1, or anti-CTLA-4 immune checkpoint ...
M.D., Ph.D., evaluated the effects of combining PS-targeting, anti-PD-1 and radiation therapies in the mouse B16 melanoma model. Study data showed that PS-targeting antibodies synergize with both anti-PD-1 and radiation therapy to improve anti-cancer activity. PS-targeting treatment in combination with radiation, as well as triple combination of PS-targeting treatment, anti-PD-1 and radiation, led to a reduction in tumor burden. Median survival for the triple combination treatment still had not been reached at the end of the 80-day observation period with other arms in the study showing median survival that ranged from 24-70 days. Researchers also evaluated the impact of the PS-targeting and radiation combination treatment on the level and type of immune activity. These results demonstrated that the combination led to a change in the tumor microenvironment, shifting it from immunosuppressive in which tumors are protected to immune active in which tumors are more susceptible to treatment. ...
PRF readers can get free access to a selected Journal of Pain paper each month, thanks to the American Pain Society. Get the free full text of the selection from the November 2017 issue here.. ...
The present invention is directed to compositions and methods to increase the expression of PD-L1 and/or IDO-1 in a population of cells, the modulated cells expressing increased PD-L1 and/or IDO-1, and methods related to the immunosuppressive effects obtained by cells expressing increased PD-L1 and/or IDO-1.
PD 0325901 | MEK1 inhibitor | PD0325901 | PD325901 | PD-0325901 | PD-325901 | CAS [391210-10-9] | Axon 1408 | Axon Ligand™ with >99% purity available from supplier Axon Medchem, prime source of life science reagents for your research
Monday U.S. Featured Earnings Agilent Technologies Inc. (NYSE: A) (Q1) EPS estimates of 48 cents, compared to 44 cents in the prior-year quarter. This week, the company announced the expanded use of Agilent´s Dako PD-L1 IHC 28-8 pharmDx ...
Pembrolizumab is an immune checkpoint inhibitor and is an anti-human programmed cell death-1 (PD-1) monoclonal antibody. Pembrolizumab is used for non-small cell lung carcinoma with high programmed cell death ligand-1 (PD-L1) expression. It has been found that better overall survival can be obtained using pembrolizumab compared to the existing chemotherapy. We report a case of perforation of small intestinal metastasis after pembrolizumab treatment. A 62-year-old man was treated by pembrolizumab for PD-L1 highly expressed lung adenocarcinoma, with multiple metastasis (small intestinal, lymph nodes, and bone). The treatment was stopped owing to drug-induced pneumonitis. One month after drug withdrawal, the patient visited the emergency department of our hospital with the complaint of severe stomachache. He had a rigid abdomen and generalized tenderness, and computed tomography scans showed free air within the abdomen. We diagnosed bowel perforation and performed emergency surgery. Surgical findings
We demonstrated that tumors from ccRCC patients with VHL biallelic inactivation (ie, loss of function) display a significant increase in PD-L1 expression compared with ccRCC tumors carrying one VHL wild-type allele. Using the inducible VHL 786-O-derived cell lines with varying hypoxia-inducible factor-2 alpha (HIF-2α) stabilization levels, we showed that PD-L1 expression levels positively correlate with VHL mutation and HIF-2α expression. Targeting HIF-2α decreased PD-L1, while HIF-2α overexpression increased PD-L1 mRNA and protein levels in ccRCC cells. Interestingly, chromatin immunoprecipitation and luciferase assays revealed a direct binding of HIF-2α to a transcriptionally active hypoxia-response element in the human PD-L1 proximal promoter in 786-O cells.. ...
Purpose: : During mouse retina maturation the final number of retinal ganglion cells (RGCs) is determined by highly regulated programmed cell death. Previous studies demonstrated that the immunoregulatory receptor programmed cell death-1 (PD-1) promotes developmental RGC death. To identify the functional signaling partner(s) for PD-1, we identified retinal expression of PD-1 ligands and examined the effect of PD-1 ligand expression on RGC number. We also explored the hypothesis that PD-1 signaling promotes development of functional visual circuitry. Methods: : Characterization of retinal and brain PD-L1 expression were examined by immunofluorescence on tissue sections. The contribution of PD-ligands to RGC number was examined in PD-ligand knockout mice. Retinal architecture was assessed by spectral domain optical coherence tomography and retinal function was analyzed by electroretinography in WT and PD-L1/L2 double deficient mice. Results: : PD-L1 expression is found throughout the neonatal ...
PCD regulates CNS cell-number homeostasis and formation of functional neuronal networks 28 29 through a balance of survival factors and death signals. 22 In particular, it has been well established that neurotrophic factors and electrical activity contribute to postnatal RGC survival. 25 30 31 32 33 34 This study introduces a distinct hypothesis that PCD may also result from an active negative selection process through the PD-1 pathway. PD-1 protein is transiently upregulated in the GCL and INL during the critical postnatal period of RGC target-finding and synaptogenesis. This spatiotemporal pattern is consistent with an important role for PD-1 receptor function in RGC culling. Our functional perturbations, using a PD-1 receptor-neutralizing antibody in vitro and PD-1-deficient mice in vivo, have demonstrated selective increases in RGC survival, thus strongly supporting a role for PD-1 signaling during the peak period of RGC physiological PCD. PD-1 is also developmentally expressed in a subset ...
In the inflamed retina, CD4(+) T-cells can cause retinal damage when they are not properly regulated. Since tissue expression of MHC Class II and co-stimulatory molecules is a key mechanism to regulate effector T-cells, we tested the hypothesis that upregulation of these proteins in the retina contributes to the regulation of CD4 T-cells. Here, we report that in retinas infected with the protozoan parasite Toxoplasma gondii MHC Class II is upregulated on infiltrating leukocytes as well as resident retinal cells including photoreceptors. Flow cytometric analysis indicated that B7 costimulatory family members (CD80, CD86, ICOS-L, and PD-L2) were not expressed on the Class II(+) cells. In contrast, PD-L1 (also named B7-H1 or CD274) was expressed on the majority of both hematopoietic and resident retinal Class II-expressing cells. Retinal cells from Toxoplasma-infected animals were able to suppress T-cell activation in a PD-L1-dependent manner. Finally, we demonstrate that MHC Class II and PD-L1 ...
The U.S. Food and Drug Administration today granted accelerated approval to Bavencio (avelumab) for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC), including those who have not received prior chemotherapy. This is the first FDA-approved treatment for metastatic MCC.. According to the National Cancer Institute, approximately 1,600 people in the United States are diagnosed with MCC every year. While the majority of patients present with localized tumors that can be treated with surgical resection, approximately half of all patients will experience recurrence, and more than 30 percent will eventually develop metastatic disease. In patients with metastatic MCC, the cancer has spread beyond the skin into other parts of the body.. Bavencio targets the programmed cell death-ligand PD-1/PD-L1 pathway with potential immune checkpoint inhibitory and anti-cancer activity. When Bavencio binds to PD-L1 it blocks the interaction of PD-L1 with its ...
Co-Author, The Evidence of Things Not Seen: Non-Matches as Evidence of Innocence, 98 Iowa L. Rev. 577 (2013). Co-Author, Toll-like receptor 7 is required for effective adaptive immune responses that prevent persistent virus infection, Cell Host Microbe., 2012 Jun.. Angelosanto JM, Blackburn SD, Crawford A, Wherry EJ, Progressive loss of memory T cell potential and commitment to exhaustion during chronic viral infection. J Virol., 2012 Aug.. Crawford A, Angelosanto JM, Nadwodny KL, Blackburn SD, Wherry EJ, A role for the chemokine RANTES in regulating CD8 T cell responses during chronic viral infection. PLoS Pathog., 2011 Jul.. Blackburn SD, et al., Tissue-specific differences in PD-1 and PD-L1 expression during chronic viral infection: implications for CD8 T-cell exhaustion. J Virol., 2010 Feb.. Shin H, Blackburn SD, et al., A role for the transcriptional repressor Blimp-1 in CD8(+) T cell exhaustion during chronic viral infection. Immunity, 2009 Aug.. Blackburn SD, et al. Co-regulation of CD8 T ...

CD274 Protein Human Recombinant | PD-L1 Antigen | ProSpecCD274 Protein Human Recombinant | PD-L1 Antigen | ProSpec

CD274 Human Recombinant produced in Sf9 Baculovirus cells is a single, glycosylated polypeptide chain containing 462 amino ... CD274 molecule, CD274 antigen, programmed cell death 1 ligand 1, PD-L1, PDCD1L1, PDCD1LG1, PDCD1 ligand 1, B7 homolog 1, B7H1. ... CD274 takes part in the costimulatory signal, vital for T-cell proliferation and creation of IL10 and IFNG, in a PDCD1- ... CD274 Human Recombinant produced in Sf9 Baculovirus cells is a single, glycosylated polypeptide chain containing 462 amino ...
more infohttps://www.prospecbio.com/cd274_protein

PathPlex™ Panel 1 (CD3E, CD8 alpha, PD-L1) | Bethyl Laboratories, Inc.PathPlex™ Panel 1 (CD3E, CD8 alpha, PD-L1) | Bethyl Laboratories, Inc.

CD274 antigen antibody. *CD3e antigen, epsilon polypeptide (TiT3 complex) antibody. *CD3e molecule, epsilon (CD3-TCR complex) ...
more infohttps://www.bethyl.com/product/A810-001

Method of treating cancer using immune checkpoint inhibitor - BRISTOL-MYERS SQUIBB COMPANYMethod of treating cancer using immune checkpoint inhibitor - BRISTOL-MYERS SQUIBB COMPANY

... antigen=CD274; Flags: Precursor," Accession No. Q9NZQ7.1, accessed at https://www.ncbi.nlm.nih.gov/protein/Q9NZQ7, accessed on ... An "antigen-binding portion" of an antibody (also called an "antigen-binding fragment") refers to one or more fragments of an ... An "anti-antigen" antibody refers to an antibody that binds specifically to the antigen. For example, an anti-PD-1 antibody ... In other embodiments, the anti-PD-1 antibody, anti-PD-L1 antibody, or antigen-binding portions thereof is a mAb or an antigen- ...
more infohttp://www.freepatentsonline.com/10544224.html

PD-L1 Antibody Panel (28-8, 73-10, SP142, CAL10) Recombinant | AbcamPD-L1 Antibody Panel (28-8, 73-10, SP142, CAL10) Recombinant | Abcam

For other IHC staining systems (automated and non-automated) customers should optimize variable parameters such as antigen ... For other IHC staining systems (automated and non-automated) customers should optimize variable parameters such as antigen ... For other IHC staining systems (automated and non-automated) customers should optimize variable parameters such as antigen ... The section was pre-treated using heat mediated antigen retrieval with EDTA buffer (pH9, epitope retrieval solution 2) for 30 ...
more infohttps://www.abcam.com/pd-l1-antibody-panel-28-8-73-10-sp142-cal10-ab239749.html

Human PD-L1 ELISA Kit, Fluorescent (ab229414) | AbcamHuman PD-L1 ELISA Kit, Fluorescent (ab229414) | Abcam

PD-L1 (also known as CD274 or B7-H1) is a membrane bound glycoprotein involved in regulation of the immune system. PD-L1 is ... Tumor antigens. * Function. Involved in the costimulatory signal, essential for T-cell proliferation and production of IL10 and ...
more infohttps://www.abcam.com/human-pd-l1-elisa-kit-fluorescent-ab229414.html?utm_source=moleculardevices.com&utm_medium=Referral&utm_campaign=CatchPoint%20SSE%7CProducts%7C43221%7CKITS/QPA%7CN%2FA%7CEng%7CN%2FA&utm_content=CatchPoint%20SSE%7C

Gene InfoGene Info

CD274 antigen. Protein Similarities Based on Shared Motif Content. Find gene products sharing protein motifs with: NP_068693 ...
more infohttps://cgap.nci.nih.gov/Genes/GeneInfo?ORG=Mm&CID=245363&LLNO=60533

CD274 (PDL1) ORF cDNA clone | Expression-ready | InvivoGenCD274 (PDL1) ORF cDNA clone | Expression-ready | InvivoGen

CD274 (PDL1) cloned gene : ORF from ATG to Stop, in pUNO1 expression plasmid selectable in E.coli and mammalian cells. Fully ... CD274 molecule.. CD274 antigen.. Programmed cell death 1 ligand 1. Back to the top ... Human CD274 isoform 1 (pUNO1-hCD274a). Genbank : NM_014143.3. ORF size : 873 bp Subclone : AgeI - NheI ... Mouse CD274 (pUNO1-mCD274). Genbank : NM_021893.2. ORF size : 873 bp Subclone : BspHI - NheI ...
more infohttps://www.invivogen.com/puno-cd274

CD274 Gene - GeneCards | PD1L1 Protein | PD1L1 AntibodyCD274 Gene - GeneCards | PD1L1 Protein | PD1L1 Antibody

CD274 Molecule, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene ... Aliases for CD274 Gene. * CD274 Molecule 2 3 5 * CD274 Antigen 2 3 4 ... Animal Models for CD274 Gene. MGI Knock Outs for CD274:. * Cd274 Cd274,tm1Lpc, ... GeneCards Summary for CD274 Gene CD274 (CD274 Molecule) is a Protein Coding gene. Diseases associated with CD274 include ...
more infohttps://www.genecards.org/cgi-bin/carddisp.pl?gene=CD274

CD274 Gene - GeneCards | PD1L1 Protein | PD1L1 AntibodyCD274 Gene - GeneCards | PD1L1 Protein | PD1L1 Antibody

CD274 Molecule, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene ... Aliases for CD274 Gene. * CD274 Molecule 2 3 5 * CD274 Antigen 2 3 4 ... Animal Models for CD274 Gene. MGI Knock Outs for CD274:. * Cd274 Cd274,tm1Lpc, ... GeneCards Summary for CD274 Gene CD274 (CD274 Molecule) is a Protein Coding gene. Diseases associated with CD274 include ...
more infohttps://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=29126

Matthew Taylor - Publications
     - Oregon Health & Science UniversityMatthew Taylor - Publications - Oregon Health & Science University

CD274 Antigen 2017 Academic cancer center phase i program development. Frankel, A. E., Flaherty, K. T., Weiner, G. J., Chen, R ...
more infohttps://ohsu.pure.elsevier.com/en/persons/matthew-taylor/publications/

Endothelial PD-L1 expression inhibits CD8 T cell-medi | Open-iEndothelial PD-L1 expression inhibits CD8 T cell-medi | Open-i

Antigens, CD274/deficiency/genetics/physiology. *CD8-Positive T-Lymphocytes/immunology. *Capillary Permeability/physiology ... E) CD8 T cells were purified from four P14-transferred mice on day 6 p.i. and mixed with chromium-labeled, antigen-pulsed MS-I ... E) CD8 T cells were purified from four P14-transferred mice on day 6 p.i. and mixed with chromium-labeled, antigen-pulsed MS-I ...
more infohttps://openi.nlm.nih.gov/detailedresult.php?img=PMC3526355_JEM_20121015_Fig4&req=4

Anti-CD274 Mouse Monoclonal Antibody (Alexa Fluor 594) [clone: 130021] | VWRAnti-CD274 Mouse Monoclonal Antibody (Alexa Fluor 594) [clone: 130021] | VWR

Learn more about Anti-CD274 Mouse Monoclonal Antibody (Alexa Fluor 594) [clone: 130021]. We enable science by offering product ... Antigen: CD274. Clonality: Monoclonal. Clone: 130021. Conjugation: Alexa Fluor 594. Epitope: Host: Mouse. Isotype: IgG1. ... Anti-CD274 Mouse Monoclonal Antibody (Alexa Fluor 594) [clone: 130021]. Supplier: Novus Biologicals ... Home , Antibodies , Anti-CD274 Mouse Monoclonal Antibody (Alexa Fluor 594) [clone: 130021] ...
more infohttps://us.vwr.com/store/product/19000493/anti-cd274-mouse-monoclonal-antibody-alexa-fluor-594-clone-130021

Svetomir Nenad Markovic, MD, PhD - Research Output
     - Mayo ClinicSvetomir Nenad Markovic, MD, PhD - Research Output - Mayo Clinic

Jeter, J. M., Bowles, T. L., Curiel-Lewandrowski, C., Swetter, S. M., Filipp, F. V., Abdel-Malek, Z. A., Geskin, L. J., Brewer, J. D., Arbiser, J. L., Gershenwald, J. E., Chu, E. Y., Kirkwood, J. M., Box, N. F., Funchain, P., Fisher, D. E., Kendra, K. L., Marghoob, A. A., Chen, S. C., Ming, M. E., Albertini, M. R. & 22 others, Vetto, J. T., Margolin, K. A., Pagoto, S. L., Hay, J. L., Grossman, D., Ellis, D. L., Kashani-Sabet, M., Mangold, A., Markovic, S. N., Nelson, K. C., Powers, J. G., Robinson, J. K., Sahni, D., Sekulic, A. D., Sondak, V. K., Wei, M. L., Zager, J. S., Dellavalle, R. P., Thompson, J. A., Weinstock, M. A., Leachman, S. A. & Cassidy, P. B., Jan 1 2018, (Accepted/In press) In : Cancer.. Research output: Contribution to journal › Article ...
more infohttps://mayoclinic.pure.elsevier.com/en/persons/svetomir-nenad-markovic/publications/

Severe nivolumab-induced pneumonitis preceding durable clinical remission in a patient with refractory, metastatic lung...Severe nivolumab-induced pneumonitis preceding durable clinical remission in a patient with refractory, metastatic lung...

Human leukocyte antigen (HLA) typing revealed HLA-A*0201 homozygosity, which is the prevalent HLA class I allele that has been ... Human leukocyte antigen (HLA) typing revealed HLA-A*0201 homozygosity, which is the prevalent HLA class I allele that has been ... Human leukocyte antigen (HLA) typing revealed HLA-A*0201 homozygosity, which is the prevalent HLA class I allele that has been ... Human leukocyte antigen (HLA) typing revealed HLA-A*0201 homozygosity, which is the prevalent HLA class I allele that has been ...
more infohttps://ucdavis.pure.elsevier.com/en/publications/severe-nivolumab-induced-pneumonitis-preceding-durable-clinical-r

Find Research Outputs
             - Kyushu UniversityFind Research Outputs - Kyushu University

Sawada, G., Niida, A., Uchi, R., Hirata, H., Shimamura, T., Suzuki, Y., Shiraishi, Y., Chiba, K., Imoto, S., Takahashi, Y., Iwaya, T., Sudo, T., Hayashi, T., Takai, H., Kawasaki, Y., Matsukawa, T., Eguchi, H., Sugimachi, K., Tanaka, F., Suzuki, H. & 24 others, Yamamoto, K., Ishii, H., Shimizu, M., Yamazaki, H., Yamazaki, M., Tachimori, Y., Kajiyama, Y., Natsugoe, S., Fujita, H., Mafune, K., Tanaka, Y., Kelsell, D. P., Scott, C. A., Tsuji, S., Yachida, S., Shibata, T., Sugano, S., Doki, Y., Akiyama, T., Aburatani, H., Ogawa, S., Miyano, S., Mori, M. & Mimori, K., May 1 2016, In : Gastroenterology. 150, 5, p. 1171-1182 12 p.. Research output: Contribution to journal › Article ...
more infohttps://kyushu-u.pure.elsevier.com/en/publications/?showAdvanced=false&allConcepts=true&inferConcepts=true&publicationYear=2010&publicationYear=2011&publicationYear=2012&publicationYear=2013&publicationYear=2014&publicationYear=2015&publicationYear=2016&publicationYear=2017&publicationYear=2018&publicationYear=2019&author=8ac3fcf1-64d7-42fe-9545-1e5f43a6d13e&format=&page=1&ordering=type&descending=false

Find Research Outputs
             - Kyushu UniversityFind Research Outputs - Kyushu University

Maehara, Y., Soejima, Y., Yoshizumi, T., Kawahara, N., Oki, E., Saeki, H., Akahoshi, T., Ikegami, T., Yamashita, Y. I., Furuyama, T., Sugimachi, K., Harada, N., Tagawa, T., Harimoto, N., Itoh, S., Sonoda, H., Ando, K., Nakashima, Y., Nagao, Y., Yamashita, N. & 17 others, Kasagi, Y., Yukaya, T., Kurihara, T., Tsutsumi, R., Takamori, S., Sasaki, S., Ikeda, T., Yonemitsu, Y., Fukuhara, T., Kitao, H., Iimori, M., Kataoka, Y., Wakasa, T., Suzuki, M., Teraishi, K., Yoshida, Y. & Mori, M., Nov 1 2019, In : International Journal of Clinical Oncology. 24, 11, p. 1333-1349 17 p.. Research output: Contribution to journal › Article ...
more infohttps://kyushu-u.pure.elsevier.com/en/publications/?showAdvanced=false&allConcepts=true&inferConcepts=true&publicationYear=2010&publicationYear=2011&publicationYear=2013&publicationYear=2014&publicationYear=2015&publicationYear=2016&publicationYear=2017&publicationYear=2018&publicationYear=2019&author=2cfdc954-8ad9-4996-9a1e-a310bb2c42dc&format=&nofollow=true

Jose (J.C.) Villasboas Bisneto, MD - Research Output
     - Mayo ClinicJose (J.C.) Villasboas Bisneto, MD - Research Output - Mayo Clinic

Next-generation immunotherapy in Lymphoma: Checkpoint blockade, chimeric antigen receptor T cells, and beyond. Villasboas ...
more infohttps://mayoclinic.pure.elsevier.com/en/persons/jose-jc-villasboas-bisneto/publications/?ordering=title&descending=false

Qinghai Ji - Research Output
     - MD Anderson Cancer CenterQinghai Ji - Research Output - MD Anderson Cancer Center

Duffy antigen receptor for chemokines in laryngeal squamous cell carcinoma as a negative regulator. Sun, G., Wang, Y., Zhu, Y ...
more infohttps://mdanderson.elsevierpure.com/en/persons/qinghai-ji/publications/?ordering=title&descending=false

Mechanisms of FUS1/TUSC2 deficiency in mesothelioma and its tumorigenic transcriptional effects | Molecular Cancer | Full TextMechanisms of FUS1/TUSC2 deficiency in mesothelioma and its tumorigenic transcriptional effects | Molecular Cancer | Full Text

Among these genes, we identified CD24 and CD274, key immunoreceptors that regulate immunogenic T and B cells and play important ... CD274, CD274 antigen; programmed cell death 1 ligand 1. -6.2. CCDC98, coiled-coil domain containing 98 ... 3). Since blocking of CD274 is now actively pursued as a novel immunotherapy [40, 41], we suggest that TUSC2 may also have ... with 10 mmol/L of sodium citrate (pH 6.0) for antigen retrieval. Peroxide blocking was done with 3% H2O2 in methanol at room ...
more infohttps://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-8-91

Strong increase of protective serum cytokines after inj | Open-iStrong increase of protective serum cytokines after inj | Open-i

Antigens, CD274. *Antigens, CD80/metabolism. *Antigens, Surface/metabolism. *Apoptosis Regulatory Proteins/metabolism ... Methodology/principal findings: Here we studied the role of the co-inhibitory molecule B7-H1 (PD-L1, CD274) on semi-mature DC ... Methodology/principal findings: Here we studied the role of the co-inhibitory molecule B7-H1 (PD-L1, CD274) on semi-mature DC ...
more infohttps://openi.nlm.nih.gov/detailedresult.php?img=PMC2875405_pone.0010800.g005&req=4

Find Research Outputs
             - University of Canberra Research PortalFind Research Outputs - University of Canberra Research Portal

Rajput, K., Chetty, G. & Davey, R., 10 Dec 2018, Proceedings - 2018 5th Asia-Pacific World Congress on Computer Science and Engineering, APWC on CSE 2018: APWConCSE 2018 . Ali, A. B. M. S., Miah, S. & Rao Valluri, M. (eds.). Danvers, USA: IEEE, Institute of Electrical and Electronics Engineers, p. 51-56 6 p. 8853828. (Proceedings - 2018 5th Asia-Pacific World Congress on Computer Science and Engineering, APWC on CSE 2018).. Research output: A Conference proceeding or a Chapter in Book › Conference contribution ...
more infohttps://researchprofiles.canberra.edu.au/en/publications/?format=&ordering=publicationYearThenTitle&descending=false&page=383

PD-L1 抗体 Panel (28-8, 73-10, SP142, CAL10) (ab239749)PD-L1 抗体 Panel (28-8, 73-10, SP142, CAL10) (ab239749)

For other IHC staining systems (automated and non-automated) customers should optimize variable parameters such as antigen ... For other IHC staining systems (automated and non-automated) customers should optimize variable parameters such as antigen ... For other IHC staining systems (automated and non-automated) customers should optimize variable parameters such as antigen ... The section was pre-treated using heat mediated antigen retrieval with EDTA buffer (pH9, epitope retrieval solution 2) for 30 ...
more infohttps://www.abcam.co.jp/pd-l1-antibody-panel-28-8-73-10-sp142-cal10-ab239749.html

Millward, M.<...Millward, M.<...

The impact of therapy on T-cell recognition of mutated tumour neo-antigens. Robinson, B., Nowak, A., Millward, M., Creaney, J. ...
more infohttps://research-repository.uwa.edu.au/en/persons/michael-millward

Programmed cell death ligand 1 (PD-L1) blockade attenuates metastatic colon cancer growth in cAMP-response element-binding...Programmed cell death ligand 1 (PD-L1) blockade attenuates metastatic colon cancer growth in cAMP-response element-binding...

TY - JOUR. T1 - Programmed cell death ligand 1 (PD-L1) blockade attenuates metastatic colon cancer growth in cAMP-response element-binding protein (CREB)-binding protein (CBP)/β-catenin inhibitor-treated livers. AU - Osawa, Yosuke. AU - Kojika, Ekumi. AU - Nishikawa, Koji. AU - Kimura, Masamichi. AU - Osakaya, Shigenori. AU - Miyauchi, Hiromi. AU - Kanto, Tatsuya. AU - Kawakami, Yutaka. AU - Kimura, Kiminori. PY - 2019/4/30. Y1 - 2019/4/30. N2 - Immune checkpoint blockade with specific antibodies can accelerate anti-tumor immunity, resulting in clinical responses in patients with various types of cancer. However, these antibodies achieve only partial tumor regression. Thus, a wide variety of treatment combinations based on programmed death-ligand 1 (PD-L1) pathway inhibition are under development to enhance such therapeutic effects. In this study, the effects of combination treatment using PRI-724, a selective inhibitor of CBP/β-catenin, and an anti-PD-L1 antibody were examined in a mouse ...
more infohttps://keio.pure.elsevier.com/en/publications/programmed-cell-death-ligand-1-pd-l1-blockade-attenuates-metastat
  • It has been assigned to the CD274 cluster of differentiation during the 8th HLDA Workshop on Human Leukocyte Differentiation Antigens, held in Adelaide, Australia, in 2004. (mybeckman.co)
  • Programmed Death- 1 (PD-1) is one of the three coinhibitory receptors with Cytotoxic T Lymphocyte Antigen 4 (CTLA4) and CD272. (mybeckman.co)
  • Human leukocyte antigen (HLA) typing revealed HLA-A*0201 homozygosity, which is the prevalent HLA class I allele that has been used to develop universal cancer vaccine targeting TERT-derived peptides. (elsevier.com)
  • Among these genes, we identified CD24 and CD274, key immunoreceptors that regulate immunogenic T and B cells and play important roles in systemic autoimmune diseases. (biomedcentral.com)
  • Except for one, the 13 functional genomic alterations remained the same in the diagnostic, recurrent, and post-treatment, relapsed tumor specimens, suggesting that nivolumab reset the patient's immune system against one or more preexisting tumor-associated antigens (TAAs). (elsevier.com)
  • CD274 Human Recombinant produced in Sf9 Baculovirus cells is a single, glycosylated polypeptide chain containing 462 amino acids (19-238a.a.) and having a molecular mass of 52.5kDa (Molecular size on SDS-PAGE will appear at approximately 50-70kDa). (prospecbio.com)
  • E) CD8 T cells were purified from four P14-transferred mice on day 6 p.i. and mixed with chromium-labeled, antigen-pulsed MS-I cells at the indicated effector to target ratios. (nih.gov)
  • Diseases associated with CD274 include Lymphoepithelioma-Like Carcinoma and Ovarian Carcinosarcoma . (genecards.org)