• Elotuzumab can stimulate robust antibody-dependent cellular cytotoxicity (ADCC) through engaging with FcγRIIIA (CD16) on NK cells and antibody-dependent cellular phagocytosis (ADCP) by macrophages. (nih.gov)
  • Further, NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) is a main immune-dependent mechanism by which tumor-targeting therapeutic mAbs mediate tumor cell killing [ 6 - 8 ]. (hindawi.com)
  • Recent studies have revealed that fucose removal from the oligosaccharides of human IgG1 antibodies results in a significant enhancement of antibody-dependent cellular cytotoxicity (ADCC) via improved IgG1 binding to FcγRIIIa. (aacrjournals.org)
  • In this report, we investigated the relationship between enhanced ADCC and antigen density on target cells using IgG1 antibodies with reduced fucose. (aacrjournals.org)
  • Using EL4 cell-derived transfectants with differential expression levels of exogenous human CC chemokine receptor 4 or human CD20 as target cells, ADCC of fucose variants of chimeric IgG1 antibodies specific for these antigens were measured. (aacrjournals.org)
  • We further investigated IgG1 binding to natural killer (NK) cells and NK cell activation during ADCC induction to elucidate the mechanism by which low-fucose IgG1 induces ADCC upon target cells with low antigen expression. (aacrjournals.org)
  • The quantitative analysis revealed that fucose depletion could reduce the antigen amount on target cells required for constant degrees of ADCC induction by 10-fold for CC chemokine receptor 4 and 3-fold for CD20. (aacrjournals.org)
  • Our data showed that fucose removal from IgG1 could reduce the antigen amount required for ADCC induction via efficient recruitment and activation of NK cells. (aacrjournals.org)
  • Antibodies of the human IgG1 isotype are commonly used for therapeutic applications as they can mediate multiple effector functions including antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and direct apoptosis induction (1-3) . (aacrjournals.org)
  • Natural killer cells are cytotoxic in nature and are able to kill their targets cells by two different mechanisms: as antibody dependent cell-mediated cytotoxicity (ADCC) and as simple natural killer activity of these cells. (openpr.com)
  • Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC): Immunoglobulins can bind to target cells, such as infected cells or cancer cells, and recruit immune cells, such as natural killer (NK) cells, to eliminate the targeted cells. (medicalbiochemist.com)
  • Historically, NK cells have been considered part of the innate immune system, recognizing and eliminating virus-infected or tumor cells either directly by release of cytotoxic granules or indirectly by cytokine release and facilitation of antibody-dependent cell-mediated cytotoxicity (ADCC). (nih.gov)
  • these include blockade, apoptosis, antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and trogocytosis. (flowmetric.com)
  • Similarly, antibody-dependent cellular cytotoxicity (ADCC) assays can measure the death of antibody-coated target cells by cytotoxic mechanisms from effector cells in PBMCs, primarily natural killer (NK) cells. (flowmetric.com)
  • One such interaction that is important to consider when designing mAB therapies is antibody-dependent cellular cytoxicity, or ADCC, a mechanism of cell-mediated immune defense whereby an immune effector cell lyses a target cell identified by bound antibodies. (asbmb.org)
  • Then, using rational mutagenesis guided by molecular dynamics, the authors showed that fragment-antigen binding region-receptor interactions directly contribute to the modulation of ADCC. (asbmb.org)
  • Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus. (ox.ac.uk)
  • Here we show that pp65, the main tegument protein of human cytomegalovirus, inhibited natural killer cell cytotoxicity by an interaction with the activating receptor NKp30. (ox.ac.uk)
  • Thus, pp65 is a ligand for the NKp30 receptor and demonstrates a unique mechanism by which an intracellular viral protein causes general suppression of natural killer cell cytotoxicity by specific interaction with an activating receptor. (ox.ac.uk)
  • NKp30/NCR3, NKp44/NCR2, and NKp46/NCR1 are termed natural cytotoxicity receptors (NCR). (bio-techne.com)
  • NK-mediated dendritic cell (DC) recognition is highly dependent on engagement of NKp30 and may result in lysis of the DC. (bio-techne.com)
  • 4. Differentiation of human peripheral blood Vδ1+ T cells expressing the natural cytotoxicity receptor NKp30 for recognition of lymphoid leukemia cells. (nih.gov)
  • 8. Influenza A Virus Hemagglutinin and Other Pathogen Glycoprotein Interactions with NK Cell Natural Cytotoxicity Receptors NKp46, NKp44, and NKp30. (nih.gov)
  • Interestingly, unlike TGF-β, activin-A weakly down-regulates the NK-cell natural cytotoxicity receptors (NCRs) NKp30 and NKG2D but does not attenuate their cytotoxic function. (ashpublications.org)
  • NK cells are an heterogeneous population harboring multiple subsets that differentially expressed NK receptors such as: killer cell immunoglobulin-like receptors (KIRs), natural killer group 2 such as NKG2A, NKG2C and NKG2D, and natural cytotoxicity receptors (NCRs), for example NKp30, NKp40 or NKp46 [ 8 , 9 ]. (encyclopedia.pub)
  • NKp46 consists of two Ig-like domains assembled to leukocyte immunoglobulin-like (LIR) and killer inhibitory receptors (KIR). (thermofisher.com)
  • In contrast, individual NK cells express, in different combinations, several inhibitory receptors (e.g. (hindawi.com)
  • In addition to modulate functional responsiveness, NK cell inhibitory receptors are critical for promoting their education [ 9 ]. (hindawi.com)
  • Killer cell inhibitory receptors. (embl.de)
  • Likewise, low expression of inhibitory human leukocyte antigen (HLA) class I molecules is an important prerequisite for successful natural killer cell triggering. (biomedcentral.com)
  • Manipulation of either the balance between activating and inhibitory signals (by, for instance, e x vivo activation of immune cells) and/or sensitization of target cells for immune-mediated killing by combination immunotherapy may improve immunotherapeutic efficacy. (biomedcentral.com)
  • Subsequently, studies on tumor-induced immune suppressive mechanisms have identified multiple suppressor cell populations and inhibitory molecules, all of which exert critical regulatory roles in tumor generation and progression ( 6 - 8 ). (frontiersin.org)
  • NK cells express inhibitory receptors (Ly49 in mice, KIR in human) that recognize class I MHC molecules and function to inhibit the lysis of cells that express class I molecules normally, and allow the destruction of those that do not. (berkeley.edu)
  • Each NK cell stably expresses 3-4 of a panel of 10 possible inhibitory receptors, which bind to partially overlapping sets of polymorphic MHC I molecules. (berkeley.edu)
  • The selection of inhibitory receptors expressed by a given NK cell is determined randomly. (berkeley.edu)
  • NK cells also express other inhibitory receptors. (berkeley.edu)
  • We have found that a fraction of NK cells within tumors frequently upregulate inhibitory checkpoint receptors, including PD-1, Lag3, and others. (berkeley.edu)
  • A ) CML cell killing by the enhancement of memory natural killer (NK) cells and cytotoxic CD8 + T cells expressing γδTCR and a reduction of inhibitory receptors driven by dasatinib. (encyclopedia.pub)
  • Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. (nih.gov)
  • 7. Role of NKG2D, DNAM-1 and natural cytotoxicity receptors in cytotoxicity toward rhabdomyosarcoma cell lines mediated by resting and IL-15-activated human natural killer cells. (nih.gov)
  • 11. NKG2D ligation without T cell receptor engagement triggers both cytotoxicity and cytokine production in dendritic epidermal T cells. (nih.gov)
  • 12. Analysis of the Expression of Surface Receptors on NK Cells and NKG2D on Immunocytes in Peripheral Blood of Patients with Nasopharyngeal Carcinoma. (nih.gov)
  • 14. Expressions of natural cytotoxicity receptors and NKG2D on decidual natural killer cells in patients having spontaneous abortions. (nih.gov)
  • 16. Expressions of natural cytotoxicity receptor, NKG2D and NKG2D ligands in endometriosis. (nih.gov)
  • Histone deacetylase inhibitor-pretreatment induced NKG2D-ligand expression in an ATM/ATR-dependent manner and sensitized for NKG2D-dependent cytotoxicity (2/4 cell lines). (biomedcentral.com)
  • Our group has investigated the role of the NKG2D receptor in tumor recognition by NK cells. (berkeley.edu)
  • NKG2D recognizes up to 8 different, though related, cell surface ligands called NKG2D ligands. (berkeley.edu)
  • NKG2D ligands are poorly expressed by normal cells, but are frequently upregulated in tumor cells and in certain infected cells. (berkeley.edu)
  • The PD-1+ NK cells are the most intrinsically active NK cells, but are inhibited if they engage tumors that express the PD-L1 ligand for NKG2D. (berkeley.edu)
  • The main activating and inhibiting NK receptors and their respective target cell ligands are shown in Figure 2 A. The NKG2C and NKG2D receptors are activating NK receptors that could detect abnormal or malignant cells by binding with HLA-E and the MIC A/B ligands, respectively. (encyclopedia.pub)
  • They can eradicate neoplastic cells by a targeted release of cytotoxic granules containing perforin and granzymes and/or death receptor-mediated killing [ 1 ]. (hindawi.com)
  • 2 In this context, targeting the Bruton tyrosine kinase (BTK), a critical non-receptor tyrosin kinase in B-cell development and activation, is a novel treatment approach apparently avoiding the cytotoxic side effects of established regimens. (haematologica.org)
  • HLH is a rare disease, characterized by impaired function of natural killer and cytotoxic T-lymphocytes that results in an unchecked inflammatory response. (cdc.gov)
  • 2. Activated gammadelta T cells express the natural cytotoxicity receptor natural killer p 44 and show cytotoxic activity against myeloma cells. (nih.gov)
  • 19. In vitro analysis of the proliferative capacity and cytotoxic effects of ex vivo induced natural killer cells, cytokine-induced killer cells, and gamma-delta T cells. (nih.gov)
  • Natural killer (NK) cells are the main cytotoxic effector cells of the innate immune system, contributing to host anti-microbial and anti-tumour immune responses. (biomedcentral.com)
  • Current research strategies aiming to prevent, control or eradicate HIV emphasize the adaptive arm of the immune system, harnessing effector functions of cytotoxic T cells, helper T cells, B cells and antibodies to attack HIV and HIV-infected cells. (nih.gov)
  • Here we explore, using live single-cell imaging, the cytotoxic functions of γδ T cells upon interactions with tumour target cells with high temporal and spatial resolution. (nature.com)
  • Thus, our data provide new insights into the cytotoxic arsenal and functions of γδ T cells, which may guide the development of more efficient γδ T cell based adoptive immunotherapies. (nature.com)
  • Single-cell RNA sequencing detected populations of Vδ1+ and Vδ2 + T cells with mature, cytotoxic phenotypes with innate features closely resembling those of natural killer (NK) cells 26 , 27 . (nature.com)
  • Unfortunately, these multidimensional approaches often face two main problems: development of resistance related to lengthy use and the presence of severe adverse effects made by the overall doses of radiation and the significant impact of cytotoxic agents on healthy cells and physiologic functions [ 1 ]. (hindawi.com)
  • Cell cycle arrest and apoptosis induced by cytotoxic agents are critical in cancer treatment ( 10 , 11 ). (spandidos-publications.com)
  • Cytotoxic cells, including natural killer (NK) cells and cytotoxic T cells, recognize and kill infected and transformed cells. (berkeley.edu)
  • Furthermore we investigate mechanisms by which tumors and infectious agents naturally activate or inhibit productive responses by cytotoxic cells, or desensitize the cells by inducing anergy. (berkeley.edu)
  • Herein, we demonstrate that the mithralog EC-7072 displays high ex vivo cytotoxic activity against leukemia cells from CLL patients independently from high-risk prognostic markers and IGHV mutational status. (frontiersin.org)
  • Low or absent natural killer (NK) cell and CD8+ cytotoxic T lymphocyte (CTL) cytotoxicity is one of the hallmarks of HLH and leads to impaired regulation of the immune response [ 4 ]. (biomedcentral.com)
  • Interestingly, off-target effects have been related to potential benefits such as an increased natural killer cell (NK)-mediated cytotoxic capacity against cancerous cells and viral infected cells [ 7 ] and an anti-aging capacity. (encyclopedia.pub)
  • Emerging treatment options, such as gene-mediated cytotoxic immunotherapy (GMCI), offer a targeted approach to cancer treatment with minimum damage to normal healthy cells. (gold-essays.com)
  • While interaction of TLR2 with mycobacterial cell wall promotes activation of resting NK cells and IFN-γ production, NKp44 interaction with its putative ligands could play a secondary role in maintaining cell activation. (ox.ac.uk)
  • Using flow cytometry, ELISA and immunohistochemistry, expression of natural killer cell receptor ligands was assessed in chemotherapy-sensitive/-resistant Ewing sarcoma cell lines, plasma and tumours. (biomedcentral.com)
  • Despite comparable expression of natural killer cell receptor ligands, chemotherapy-resistant Ewing sarcoma exhibited reduced susceptibility to resting natural killer cells. (biomedcentral.com)
  • Sensitivity of tumours to natural killer cells critically depends on expression of ligands for activating receptors. (biomedcentral.com)
  • For example, pre-conditioning of various cancer cell types by agents that activate the DNA damage response pathway may sensitize for natural killer cell cytotoxicity via induction of activating natural killer cell receptor ligands and/or death receptor expression. (biomedcentral.com)
  • 10 , 11 We recently have shown that as well as producing IL-12p70, activated DCs also rapidly secrete high levels of activin-A after exposure to bacteria, specific Toll-like receptor (TLR) ligands, or CD40 ligand (CD40L). (ashpublications.org)
  • Elotuzumab is a humanized IgG1 monoclonal antibody targeting SLAMF7, which is highly expressed on myeloma cells, and the antibody is approved for the treatment of relapsed and/or refractory (RR) MM in combination with lenalidomide and dexamethasone. (nih.gov)
  • Accumulating evidence indicates that antibody crosslinking of SLAMF7 on human and mouse NK cells can stimulate EAT-2-dependent activation of PLCγ, ERK, and intracellular calcium mobilization. (nih.gov)
  • [ 7 ] The Fc domain triggers immune effector functions by interacting with Fc receptors, c-type lectins or the complement system to ensure that antibody-opsonized material can additionally be visualized and appropriately eliminated by the immune system. (medscape.com)
  • Up-regulation of an activation marker, CD69, on NK cells, particularly the CD56 dim subset, in the presence of both the antibody and target cells was much greater for the low-fucose antibodies. (aacrjournals.org)
  • Immunohistochemical techniques using monoclonal antibody recognition of B and T cells have been shown to solve this problem in various pathological conditions [9-11]. (who.int)
  • The efficacy of a therapeutic antibody depends on the Fab fragment and its binding activity to the target antigen, but also depends on the Fc fragment and its interaction with key Fc receptors.Therefore, candidates must be tested against a panel of receptors during antibody engineering. (acrobiosystems.com)
  • The graph titled "Effect of HER2 antibody plus sialidase on immune activity" is from an experiment with laboratory-cultured populations of ZR-75-1 human breast cancer cells, which compared with normal breast cells have elevated (but not astronomical) levels of the HER2 protein on their surfaces. (sciencenews.org)
  • These types of flow cytometry assays are compatible with the assessment of almost all antibodies / antibody-derivatives and cell types and are therefore ideal for translational, preclinical, and clinical studies (Miller, M and Finn, O. 2020). (flowmetric.com)
  • The blockade is a frequently observed mechanism by which a therapeutic antibody interferes with the binding of a target cell receptor or surface molecule and therefore blocks downstream immunological responses (e.g., immune checkpoint inhibitors). (flowmetric.com)
  • Flow Cytometry-based assays for apoptosis can be used to track and quantify the effect of an experimental antibody on target cells within a heterogeneous population through a variety of different biomarkers. (flowmetric.com)
  • Antibody-dependent cellular phagocytosis (ADCP) can be measured in a variety of ways by flow cytometry but essentially target and effector cells are independently labeled, and the test antibodies are then added. (flowmetric.com)
  • CDC assays are frequently employed to determine the efficacy of antibody-based therapeutics and their capacity to initiate multiple facets of the immune system to kill targeted cells (Gancz, D. and Fishelson, Z, 2009), as well as assess xeno-transplants. (flowmetric.com)
  • However, recent studies on antibody-mediated killing responses against tumor cells and the generation of a huge number of antibodies against antitumor response helped produce monoclonal antibody (mAb) for recognizing specific antigens available on the surface of cancer cells. (hindawi.com)
  • Antibody interactions that change cytotoxicity. (asbmb.org)
  • therefore, understanding how antibody-receptor interactions influence effector function is important for mAB design. (asbmb.org)
  • For instance, R&D Systems offer a wide range of reagents for culturing natural killer cells and investigating natural killer cell and tumor cell interactions and various other components such as recombinant proteins, blocking/neutralization antibodies, fluorochrome-conjugated antibodies and ELISA Kits. (openpr.com)
  • These receptors are type I transmembrane proteins with 1-2 extracellular immunoglobulin domains, a transmembrane domain containing a positively charged amino acid residue, and a short cytoplasmic tail. (bio-techne.com)
  • Explore our comprehensive collection of recombinant Fc receptor proteins! (acrobiosystems.com)
  • The induction of apoptosis is correlated with the expression of several cell surface proteins referred to as death receptors (DRs)- these include CD95 (FAS), CD261, CD262 (DR5/TRAIL-R2), CD120a (TNF-R1), CD120b, all of which can be detected with fluorophore-conjugated antibodies using flow cytometry. (flowmetric.com)
  • The cell cycle and apoptosis were evaluated using flow cytometry analysis, and proteins were detected using western blotting. (spandidos-publications.com)
  • They encode the proteins perforin, MUNC13-4, syntaxin-11 and MUNC18-2, all of which play a key role in lymphocyte cytotoxicity (Figure 1 ) [ 14 ]. (biomedcentral.com)
  • Although 1 affects different signaling pathways in different cell lines and has multiple functions, we have identified its target proteins, which explain and clarify the universal mechanism of its medicinal efficacy. (nature.com)
  • Taken together, these results support the hypothesisthat basigin-2 can function as a receptor for soluble basigin and demonstratethat the hemophilic interactions between basigin proteins are not dependentupon glycosylation of the basigin ligand. (illinois.edu)
  • In NK effector cells, cytotoxicity is induced through lytic vesicles which fuse with the effector plasma membrane. (nature.com)
  • A promising approach to engage effector cells of the immune system overcoming some of the escape mechanisms has been introduced more than two decades ago. (mdpi.com)
  • 4 DCs detect pathogens via an array of pattern-recognition receptors 5 and pathogen encounter induces DC maturation and production of proinflammatory chemokines and cytokines such as interferon-induced protein (IP)-10, interleukin (IL)-8, IL-6, tumor necrosis factor α (TNF-α), IFN-α, and IL-12, 6 , 7 which attract and activate innate effector cells. (ashpublications.org)
  • Apoptosis (derived from the Greek word 'apo plus ptosis' meaning 'falling off') is a process of events characterized by initial cell shrinkage, increased cell permeability through membrane disruption, chromatin condensation leading to DNA fragmentation, and finally cell blebbing and the removal of the apoptotic cells by phagocytosis. (flowmetric.com)
  • There is growing evidence that apoptosis may represent a key step in the development of immunity, and apoptotic cells are thought to be a source of immunological instructions that may influence many different mechanistic pathways of the immune system (Albert 2004). (flowmetric.com)
  • It was demonstrated that pemetrexed inhibited cell survival and induced G0/G1 cell cycle arrest and apoptosis in human ESCC cells. (spandidos-publications.com)
  • Furthermore, the results demonstrated that the phorbol‑12‑myristate‑13‑acetate‑induced protein 1/induced myeloid leukemia cell differentiation protein Mcl‑1 axis is involved in intrinsic apoptosis induced by pemetrexed. (spandidos-publications.com)
  • Members of the apoptosis regulator Bcl-2 (Bcl-2) family serve crucial roles in the regulation of apoptotic processes in various cancer cells ( 12 ). (spandidos-publications.com)
  • NOXA is able to interact with the anti-apoptotic Bcl-2 protein induced myeloid leukemia cell differentiation protein Mcl-1 (Mcl-1), interfering with the polymerization of apoptosis regulator BAX and Bcl-2 homologous antagonist/killer to trigger the mitochondrial apoptosis pathway ( 14 ). (spandidos-publications.com)
  • Panobinostat (LBH589) induces apoptosis through the regulation of specificity protein 1 (Sp1) in the oral squamous cell carcinoma (OSCC) cell lines, HN22 and HSC4. (spandidos-publications.com)
  • LBH589 significantly reduced cell growth and the sub-G1 cell population and induced apoptosis. (spandidos-publications.com)
  • Taken together, our data demonstrate that LBH589 induces the apoptosis of OSCC cells by suppressing Sp1 expression, indicating that LBH589 may be a promising chemotherapeutic agent for the treatment of OSCC. (spandidos-publications.com)
  • Specifically, HDAC inhibitors have been linked to several downstream effects in tumor cell lines, resulting in cell cycle arrest and the induction of apoptosis ( 9 - 11 ). (spandidos-publications.com)
  • We demonstrate that LBH589 inhibits cell growth and induces apoptosis in the HN22 and HSC4 cells. (spandidos-publications.com)
  • EC-7072 directly triggered caspase-3-dependent CLL cell apoptosis, which was not abrogated by microenvironment-derived factors that sustain leukemia cell survival. (frontiersin.org)
  • Astrocytes exposed to 2, 3, and 4 h of OGD exhibited increased cell injury and apoptosis, and the protein levels of caspase-12, cleaved caspase-3, NLRP3 inflammasome components, and IL-1β were also significantly elevated. (medsci.org)
  • Interestingly, pretreatment with the caspase-12-specific inhibitor Z-ATAD-FMK attenuated cell injury and apoptosis and decreased the levels of NLRP3, caspase-1, IL-1β, and cleaved caspase-3 in the OGD group. (medsci.org)
  • Experiments have shown that caspase-12 is responsible for further activation of caspase-3 and ERS-induced cell apoptosis in astrocytes following ischemic stroke [ 5 - 7 ]. (medsci.org)
  • Flow cytometry and Western blot were utilized to investigate cell apoptosis. (ijpsonline.com)
  • Harpagide up-regulates microRNA-140-5p to inhibit the oxidative stress and apoptosis of oxidized low-density lipoprotein-induced human umbilical vascular endothelial cells. (ijpsonline.com)
  • Studies have shown that harpagide may inhibit Aβ25-35 induced apoptosis and oxidative stress of PC12 cells through activation of Phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase B (Akt) signaling pathway, indicating its potential value in the treatment of Alzheimer's disease[ 7 ]. (ijpsonline.com)
  • IL-7 assists in the development of lymphocytes and regulates peripheral T-cell populations [ 2 ]. (jcancer.org)
  • The results showed that the dense lymphocytic infiltrate surrounding neoplastic cells of BCC consisted chiefly of T-lymphocytes. (who.int)
  • Natural killer cells are a form of granular lymphocytes of varying sizes that play an important role in innate immunity in the human body. (openpr.com)
  • They typically constitute of around 10% of total blood lymphocytes as compared to around 70% and 20% of T cells and B cells, respectively. (openpr.com)
  • 10. Human gammadelta T lymphocytes induce robust NK cell-mediated antitumor cytotoxicity through CD137 engagement. (nih.gov)
  • In contrast to T-lymphocytes, these cells lack antigen-specific receptors. (biomedcentral.com)
  • It is estimated that T cells associated with the small intestinal epithelium alone may account for more than 60% of the total body lymphocytes. (prn.org)
  • NKp46 (CD335, NCR1, ) is a cytotoxicity-activating receptor that may contribute to the increased efficiency of activated natural killer (NK) cells to mediate tumor cell lysis. (thermofisher.com)
  • Upon reinfection, these memory NK cells undergo secondary expansion, rapidly degranulate, and release cytokines, leading to a protective immune response, and also provide protection to newborn mice challenged with MCMV, upon adoptive transfer [ 16 ]. (hindawi.com)
  • Anti-human NCR3 mAb, is derived from hybridization of mouse F0 myeloma cells with spleen cells from BALB/c mice immunized with a recombinant human NCR3 protein 19-138 amino acids purified from E. coli. (prospecbio.com)
  • We show that bacteria-induced colon cancer is accompanied by differential accumulation of IL-17(+)IL-22(+) colonic innate lymphoid cells (cILCs), which are phenotypically distinct from LTi and NK-22 cells, and that their depletion in mice with dysplastic inflammation blocks the development of invasive colon cancer. (ox.ac.uk)
  • Cell surface receptors containing an immunoglobin domain. (embl.de)
  • Triggers cytolytic activity only in natural killer cells (NK) expressing high surface densities of natural cytotoxicity receptors (PubMed:11489943, PubMed:16920955). (nih.gov)
  • Killer cell also work through another approach of direct recognition of pathogen derived structures on the surface of the infected cell. (openpr.com)
  • The MHC genes are codominantly expressed, which means that each individual expresses these genes from both the alleles on the cell surface. (medscape.com)
  • We have previously demonstrated that a soluble form of the human NK cell natural cytotoxicity receptor NKp44, binds to the surface of Mycobacterium tuberculosis (MTB). (ox.ac.uk)
  • The B-cell receptor consists of an Ig molecule anchored to the cell's surface. (msdmanuals.com)
  • Chronic lymphocytic leukemia (CLL), the most common leukemia in adults in western countries, is characterized by the progressive accumulation of mature-appearing clonal B cells expressing CD5, CD23, and CD19 surface markers in the blood, bone marrow and secondary lymphatic tissues. (frontiersin.org)
  • 1 Having such a large surface in close proximity to the external environment necessitates that a large complement of immune cells-both innate and adaptive-be deployed at mucosal surfaces. (prn.org)
  • Then, the extracts were screened on HSV-1 surface glycoproteins and host cell surface receptors for potential binding ability by molecular docking, which further verified the phenotypic results. (biomedcentral.com)
  • Attempts to demonstrate specifichemophilic on separate cells, or between soluble forms of recombinant basiginusing surface Plasmon resonance have not been successful, suggesting thatbasigin-2 cannot function as a receptor for itself. (illinois.edu)
  • Small-interfering RNA (siRNA)knockdown of basigin-2 protein reduced, but did not eliminate, rBSG-mediatedERK activation in HESCs, suggesting that additional cell surface receptors forsoluble basigin may exist. (illinois.edu)
  • CD94/NKG2A and killer immunoglobulin-like receptors (KIR)) that recognize MHC class I molecules. (hindawi.com)
  • 18. Human NK cells selective targeting of colon cancer-initiating cells: a role for natural cytotoxicity receptors and MHC class I molecules. (nih.gov)
  • Interaction of Mycobacterium tuberculosis cell wall components with the human natural killer cell receptors NKp44 and Toll-like receptor 2. (ox.ac.uk)
  • Herein, we investigated the interaction of MTB cell wall components (CWC) with NKp44 or with Toll-like receptor 2 (TLR2) and the role of NKp44 and TLR2 in the direct activation of NK cells upon stimulation with MTB CWC. (ox.ac.uk)
  • By using several purified bacterial CWC in an ELISA, we demonstrated that NKp44 was able to bind to the MTB cell wall core mycolyl-arabinogalactan-peptidoglycan (mAGP) as well as to mycolic acids (MA) and arabinogalactan (AG), while soluble TLR2 bound to MTB peptidoglycan (PG), but not to MA or AG. (ox.ac.uk)
  • The mAGP complex induced NK cell expression of CD25, CD69, NKp44 and IFN-γ production at levels comparable to M. bovis Bacillus Calmette-Guérin-stimulated (BCG) cells. (ox.ac.uk)
  • Activation of resting NK cells by mAGP and IFN-γ production were inhibited by anti-TLR2 MAb, but not by anti-NKp44 MAb. (ox.ac.uk)
  • Differently, anti-NKp44 MAb partially inhibited CD69 expression on NK cells pre-activated with IL-2 and then stimulated with mAGP or whole BCG. (ox.ac.uk)
  • Overall, these results provide evidence that components abundant in mycobacterial cell wall are able to interact with NKp44 (AG, MA) and TLR-2 (PG), respectively. (ox.ac.uk)
  • NKp44 is induced upon activation of resting NK cells with IL-2 and can bind to viral hemagglutinins. (bio-techne.com)
  • In particular, NK-derived IFN- γ stands as a well-recognized key immunoregulatory factor in the shaping of antitumor adaptive immune responses, by modulating dendritic cell (DC) and T cell responses [ 3 - 5 ]. (hindawi.com)
  • In lymph nodes (LNs), dendritic cells (DCs) are thought to dispose of apoptotic cells, a function pertaining to macrophages in other tissues. (bvsalud.org)
  • Conversely, the innate immune system, including epithelial barriers, the complement system, phagocytes, dendritic cells (DCs) and Natural Killer (NK) cells, provides a much more rapid and less specific response to infection. (nih.gov)
  • NK cells can modulate the magnitude and quality of adaptive immune responses by interacting with, editing or killing dendritic cells or B and T cells, thereby bridging the innate and adaptive immune responses. (nih.gov)
  • Dendritic-cell (DC) and natural killer (NK)-cell interactions are critical in sculpting the adaptive immune response. (ashpublications.org)
  • 1-3 NK cells also play an important role in the regulation of both innate and adaptive immunity via direct interaction with dendritic cells (DCs) in the lymph node or within inflamed tissues via production of interferon (IFN)-γ. (ashpublications.org)
  • Natural cytotoxicity triggering receptor 2 is a protein that in humans is encoded by the NCR2 gene. (wikipedia.org)
  • Interestingly, SLAMF7 is also expressed on cytolytic NK cells, which also express the requisite adaptor protein, EAT-2, to mediate activation signaling. (nih.gov)
  • Interleukin-7 (IL-7) is an immunopotent regulatory protein produced by stromal cells and by several different inflammatory cells [ 1 ]. (jcancer.org)
  • the influence of the protein upon the tumor cell proliferation is unclear [ 3 ]. (jcancer.org)
  • My lab studies how cells use RNA-protein interactions to regulate gene expression. (nih.gov)
  • Neural factors are a class of protein molecules with neurotrophic activity that can promote the survival and regeneration of nerve cells. (acrobiosystems.com)
  • HER2 protein is a growth factor receptor, which helps to sense signals from the environment telling cells to grow. (sciencenews.org)
  • Using anti-Zika virus assays, the authors showed that seven of the 30 compounds inhibited Zika virus RNA replication and nonstructural protein 5 production in Zika-infected A549 cells. (asbmb.org)
  • The results from the present study provide experimental evidence to support the hypothesis that LBH589 decreases specificity protein 1 (Sp1) expression and inhibits OSCC cell viability by inducing cell cycle arrest and activating apoptotic pathways. (spandidos-publications.com)
  • This article summarizes recent evidence in the literature on the peculiar features that render memory NK cells an attractive tool for antitumor immunotherapy, including their long-term survival and in vivo persistence, the resistance to tumor-dependent immunosuppressive microenvironment, the amplified functional responses to IgG-opsonized tumor cells, and in vitro expansion capability. (hindawi.com)
  • NK cells represent a pivotal player of innate antitumor immune responses. (hindawi.com)
  • Recent studies have reported that pemetrexed is also able to act as an antitumor drug, and its cytotoxicity has been demonstrated in advanced non-small cell lung cancer and malignant pleural mesothelioma ( 8 , 9 ). (spandidos-publications.com)
  • Cytotoxicity Triggering Receptor 3 also known as NCR3 is a natural cytotoxicity receptor (NCR) which assists NK cells in the lysis of tumor cells. (prospecbio.com)
  • Furthermore, pro-inflammatory cytokines are secreted by activated natural killer cells, which then trigger Perforin/Granzyme induced target cell lysis. (openpr.com)
  • Complement-dependent cytotoxicity (CDC) assays are used to quantify the death of target cells bound with antibodies that interact with components of the complement system and activate the complement cascade, resulting in target cell lysis. (flowmetric.com)
  • Here we review these different subsets with particular emphasis on the recently described T cell zone MΦ. (bvsalud.org)
  • 17. Spontaneous and natural cytotoxicity receptor-mediated cytotoxicity are effector functions of distinct natural killer subsets in hepatitis C virus-infected chimpanzees. (nih.gov)
  • After allogeneic hematopoietic cell transplantation, frequencies of the γδ T cell subsets in the stem cell graft influence the treatment outcome as higher proportions of CD8+ γδ T cells are associated with increased incidence of acute graft versus host disease 22 . (nature.com)
  • Cell-wall β-glucans from natural sources including plant, fungi, and bacteria are molecules that adopt pathogen-associated molecular pattern (PAMP) known to target specific receptors on immune cell subsets. (frontiersin.org)
  • Methods We developed a GMP-compliant protocol to expand adaptive NK cells from cryopreserved cells derived from select third-party superdonors, that is, donors harboring large adaptive NK cell subsets with desired KIR specificities at baseline. (bmj.com)
  • Such receptor engages its ligand when a natural killer cell encounters any normal cell that leads to generation of signal triggered, which in turn stimulates the natural killer cells to carry out its process. (openpr.com)
  • The global natural killer cells market is highly competitive and fragmented, though companies are investing of specific therapy using natural killer cell products to be used in immune-oncology to treat cancer and other tumors. (openpr.com)
  • A subclass of natural killer cell receptors that perform an important role in the recognition of tumor cells by NK CELLS. (bvsalud.org)
  • We evaluated the susceptibility of Ewing sarcoma to natural killer cell-based combination immunotherapy, by assessing the capacity of histone deacetylase inhibitors to improve immune recognition and sensitize for natural killer cell cytotoxicity. (biomedcentral.com)
  • Natural killer cell cytotoxicity was evaluated in Chromium release assays. (biomedcentral.com)
  • 3 While inherited genetic defects in the Btk gene cause X-linked agammaglobulinemia (XLA), inhibition by the small compound ibrutinib down-regulates B-cell receptor signaling by suppressing B-cell receptor overstimulation and subsequently B-cell activation in normal and malignant B cells. (haematologica.org)
  • We have employed our understanding of NK recognition, activation and inhibition to establish therapy combinations that super-activate NK cells, while at the same time preventing desensitization and inhibition of the cells. (berkeley.edu)
  • NK cell inhibition by KIR/Ly49 and checkpoint receptors. (berkeley.edu)
  • Vascular endothelial cell dysfunction is initial process of atherosclerosis[ 3 ] and inhibition of vascular endothelial cell injury is helpful for atherosclerosis therapy. (ijpsonline.com)
  • We studied the adaptive state of the cell product (ADAPT-NK) by flow cytometry and mass cytometry as well as cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq). (bmj.com)
  • We investigated the functional responses of ADAPT-NK cells against a wide range of tumor target cell lines and primary AML samples using flow cytometry and IncuCyte as well as in a mouse model of AML. (bmj.com)
  • Blockade can be monitored using different flow cytometry-based approaches such as receptor occupancy assays. (flowmetric.com)
  • Moreover, NCR3 interacts with CD3-zeta (CD247), a T-cell receptor. (prospecbio.com)
  • Moreover, NK cells can signal to other immune cells by producing cytokines and chemokines, such as IFN- γ , TNF α , IL-6, GM-CSF, and CCL5 in response to target cells or cytokine stimulation [ 1 , 2 ]. (hindawi.com)
  • and (3) suppressing NK-cell CD25 expression and proliferation and sculpting NK-cell cytokine and chemokine profiles. (ashpublications.org)
  • SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. (nih.gov)
  • The purpose of this Funding Opportunity Announcement (FOA) is to foster interdisciplinary basic, translational, and clinical research that will define Natural Killer (NK) cell functions and interactions with other components of the innate and adaptive immune system affecting the potency and durability of HIV-1-specific immunity, including vaccine efficacy, reservoir size, reactivation or post-treatment control. (nih.gov)
  • The secondary immune defect as the underlying cause of frequent infections is in part due to hypoimmunoglobulinemia or diminished T- and B-cell responses suppressing protective immunity. (haematologica.org)
  • These findings provide the first evidence for a novel immune regulatory role of activin-A during DC-mediated NK-cell regulation, highlighting the potential of antagonizing activin-A signaling in vivo to enhance NK cell-mediated immune functions and adaptive immunity. (ashpublications.org)
  • DC-derived IL-12p70 can act as a potent cofactor for enhancing NK-cell cytotoxicity and IFN-γ production, which is responsible for the initial shaping of T-helper type 1 (Th-1) immunity. (ashpublications.org)
  • Within the MLNs, lymphoid cells from mucosal and systemic immunity interact, T-cell maturation continues, and it is likely that critical issues of gut homeostasis are determined as outlined below. (prn.org)
  • In order to gain more insight into the tumour-host relationship, the present study was conducted to characterize the in situ phenotype of the lymphocytic infiltrate surrounding tumour tissue of BCC through the use of monoclonal antibodies against B and T cell populations. (who.int)
  • Positive signaling in NK cells implicates phosphorylation of VAV1. (nih.gov)
  • Mechanistic analyses showed that IL-22 selectively acts on epithelial cells to induce Stat3 phosphorylation and proliferation. (ox.ac.uk)
  • Crosslinking-mediated BCR activation antagonized CLL cell death triggered by EC-7072, increased the phosphorylation levels of the abovementioned signaling nodes and upregulated BCL2 expression, suggesting that the mithralog disrupts CLL cell viability by targeting the BCR signaling axis at multiple levels. (frontiersin.org)
  • Here, we identify cells within human adult secondary lymphoid tissues that are comparable in phenotype and location to the lymphoid tissue inducer (LTi) cells that persist in the adult mouse. (nih.gov)
  • Combined, these data indicate that the CD117(+) CD3(-) CD56(-) OX40L(+) cells in human secondary lymphoid tissues are comparable in phenotype, location and function to the LTi cells that persist within adult murine secondary lymphoid tissues. (nih.gov)
  • Protection in these models is mediated by Ly49H + NK cells, which upon recognition of m157 viral antigen (Ly49H ligand) proliferate and persist in lymphoid and nonlymphoid organs. (hindawi.com)
  • However, among patients from Asia and South America, such lesions often show atypical lymphoid cells. (openpr.com)
  • Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model. (ox.ac.uk)
  • Peyer's patches have the anatomic appearance of secondary lymphoid organs, with clearly defined T- and B-cell-dependent areas. (prn.org)
  • The self-tolerance mechanism (also called NK cell "licensing") represents a tuning mechanism that sets the triggering threshold of individual NK cells so as to maximize reactivity against unhealthy cells while preventing reactivity against self cells, and works by desensitizing autoreactive NK cells. (berkeley.edu)
  • NK receptors are differentially expressed, creating a diverse population with multiple specificities and functions. (nih.gov)
  • Immunoglobulins evolved to specifically recognize target structures (antigens) mediated by the fragment antigen-binding (Fab) domains, while the fragment crystallizable (Fc) domain contains the binding sites for immune effector molecules such as the C1q component of the complement system and through binding to Fc receptors. (medscape.com)
  • While γδ T cell killing is dominated by degranulation, the availability of lytic molecules appears tightly regulated in time and space. (nature.com)
  • Overview of the Immune System The immune system distinguishes self from nonself and eliminates potentially harmful nonself molecules and cells from the body. (msdmanuals.com)
  • EC-7072 was significantly less toxic against T cells and NK cells and did not alter the production of the immune effector molecules IFN-γ and perforin. (frontiersin.org)
  • Studies have also been carried to express the vitality of natural killer cells' response against infected cells by various intracellular bacteria such as Listeria, Salmonella and Legionella in humans. (openpr.com)
  • Those cells have been referred to as melanophages in humans. (bvsalud.org)
  • Some of these findings were recapitulated in humans and used to develop cancer immunotherapies based on provoking tumor-antigen-specific T-cell responses ( 4 , 5 ). (frontiersin.org)
  • in such context, memory NK cells have been initially identified in healthy HCMV-seropositive individuals, mainly on the basis of high expression levels of CD94/NKG2C activating receptor and CD57 terminal differentiation marker [ 17 - 21 ]. (hindawi.com)
  • Current treatments are hampered by variability in NK cell subset responses, a limitation which could be circumvented by specific expansion of highly potent single killer immunoglobulin-like receptor (KIR) + NKG2C + adaptive NK cells to maximize missing-self reactivity. (bmj.com)
  • The first demonstration of antigen-specific recall responses by NK cells was in the setting of hapten-induced contact hypersensitivity, where CXCR6 + liver-derived murine NK cells could mediate antigen-specific contact hypersensitivity independently from B and T cells [ 13 , 14 ]. (hindawi.com)
  • Binding of these antibodies to their receptors is a core component of the innate immune system, and understanding the interaction between antibodies and their Fc receptors - which interact with the tail, or Fc, region of antibodies - is essential for the engineering of effective mAB biotherapeutics. (asbmb.org)
  • EC-7072 exerted similar or higher antileukemic activity than that of several available CLL therapies and displayed additive or synergistic interaction with these drugs in killing CLL cells. (frontiersin.org)
  • Importantly, BTK is not only relevant in B cells, but also in innate immune cells such as polymorphonuclear neutrophils (PMN) and macrophages. (haematologica.org)
  • However, the immune cells and cytokines that mediate the transition from intestinal inflammation to cancer are poorly understood. (ox.ac.uk)
  • Opsonization: Immunoglobulins can coat bacteria or other pathogens, marking them for recognition and phagocytosis by immune cells such as macrophages and neutrophils. (medicalbiochemist.com)
  • Natural killer (NK) cells are innate immune cells specialized in the recognition and killing of virus-infected or tumor cells. (ashpublications.org)
  • The mechanisms are central to how NK cells function, and are likely also important for understanding a variety of developmental decisions in immune cells and other lineages. (berkeley.edu)
  • The largest reservoir of immune cells in the body. (prn.org)
  • Immune cells in the GI tract are organized into distinct anatomic and functional subcompartments (Figure 1). (prn.org)
  • Engagement of a ligand on an unhealthy cell causes the NK cell to kill it and secrete cytokines. (berkeley.edu)
  • We found that the myeloid cells of the ear skin dermis are dominated by DT-sensitive, melanin-laden cells that have been missed in previous studies and correspond to macrophages that have ingested melanosomes from neighboring melanocytes. (bvsalud.org)
  • Benefiting of our knowledge on melanophage dynamics, we determined the identity, origin, and dynamics of the skin myeloid cells that capture and retain tattoo pigment particles. (bvsalud.org)
  • CML is a hematopoietic progenitor cell leukemia, in which overgrown myeloid cells accumulate in bone marrow and peripheral blood [ 2 ]. (encyclopedia.pub)
  • 13. Quantitative analysis of human NK cell reactivity using latex beads coated with defined amounts of antibodies. (nih.gov)
  • Importantly, these cells were not an NK cell subset since they showed no expression of IFN-γ and perforin. (nih.gov)
  • In particular, the limited co-occurrence of granzyme B and perforin restrains serial killing of tumour cells by γδ T cells. (nature.com)
  • Identified as CD117(+) CD3(-) CD56(-) cells, like murine LTi cells, they lack expression of many common lineage markers and express CD127, OX40L and TRANCE. (nih.gov)
  • Furthermore, like murine LTi cells, these cells expressed high levels of IL-22 and upregulated IL-22 expression upon IL-23 stimulation. (nih.gov)
  • Here we describe a new mouse model that exploits the pattern of expression of the high-affinity IgG receptor (CD64) and allows diphtheria toxin (DT)-mediated ablation of tissue-resident macrophages and monocyte-derived cells. (bvsalud.org)
  • We think that this mechanism generally allows cells to maintain tight control over gene expression. (nih.gov)
  • 9. Differential expression of natural killer receptors on Vdelta1 gammadelta T cells in HIV-1-infected individuals. (nih.gov)
  • We hypothesized that gene expression profiling may discriminate vanadium from zinc in human bronchial epithelial cells (HBECs). (nih.gov)
  • demonstrated distinct expression patterns in human lung cells exposed to low and high doses of arsenic. (nih.gov)
  • Although NK cells are considered components of the innate immune response, we discovered that they have the potential to attack self cells (e.g. self cells that lack MHC I expression). (berkeley.edu)
  • It has been shown that EMMPRIN expression is linked to various cell signaling pathways that lead to an increase in tumor cell vascularization. (illinois.edu)
  • Along with highlighting these issues, we speculate that memory NK cell-based adoptive immunotherapy settings would greatly take advantage from the combination with tumor-targeting therapeutic antibodies (mAbs), as a strategy to fully unleash their clinical efficacy. (hindawi.com)
  • Overall, our findings provide rationale for future investigation to test whether EC-7072 may be a potential therapeutic option for patients with CLL and other B-cell malignancies. (frontiersin.org)
  • However, the use of routine endomyocardial biopsy in establishing the diagnosis of myocarditis rarely is helpful clinically, since histologic diagnosis seldom has an impact on therapeutic strategies, unless giant cell myocarditis is suspected. (medscape.com)
  • The potential immunomodulatory effects of dasatinib on NK cells and other innate cells and its therapeutic role against CML, HIV infection and aging ( Figure 1 ). (encyclopedia.pub)
  • To date, the use of conventional synthetic chemotherapeutic drugs lack the properties to be considered as effective therapeutic agents, with most of those associated with severe side effects and toxicity of the normal host cells. (sciepub.com)
  • Whereas an alternative therapeutic approach that uses natural plant extracts is advantageous vs conventional therapy with limited side effects. (sciepub.com)
  • It has also been shown that soluble EMMPRIN binds tomembrane-bound EMMPRIN and the bound complex is internalized presenting apotential means to deliver therapeutic compounds to the cell in a highlytargeted manner. (illinois.edu)
  • Natural killer cells play an important role in stem-cell transplantation in therapies involving such cells activating endogenous natural killer cells and may transfer exogenous cells through adoptive cell therapy (ACT) and hematopoietic stem cell transplantation (HSCT). (openpr.com)
  • In patients with predisposing genetic disease, hematopoietic stem cell transplantation is performed increasingly with reduced intensity conditioning regimes. (biomedcentral.com)
  • These strategies include eliminating tumor bulk to provoke the release of tumor antigens, using adjuvants to enhance antigen-presenting cell function, and employ agents that enhance immune cell effector activity. (frontiersin.org)
  • Preclinical animal studies have identified tumor-specific antigens and the direct killing of tumor cells using T cells specific for these antigens ( 2 , 3 ). (frontiersin.org)
  • B cells The immune system consists of cellular components and molecular components that work together to destroy antigens. (msdmanuals.com)
  • 3 These are classified as immune inductive sites, considered as sites of T cell education, and immune effector sites, where T cells neutralize foreign antigens-both microbial and nonmicrobial. (prn.org)
  • The FDA subsequently expanded the approved use of nivolumab to patients with advanced squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy in 2015 ( 12 ). (frontiersin.org)
  • and, in response to antigen, are subsequently secreted by plasma cells. (msdmanuals.com)
  • Immunoprecipitation studies using cell fractions revealed thatrBSG interacts with basigin-2 at the cell membrane, and subsequently interactswith the basigin-3 isoform within the cell. (illinois.edu)
  • Immunotherapy has blossomed as a treatment option with enormous potential to avert or suppress cancer progression due to its direct influence on malignant cells with superior efficiency to target and attack the cancer cells [ 2 ]. (hindawi.com)
  • 2011). Unfortunately, the majority of cancer survivors fear cancer recurrence because it is common for malignant cells to become resistant to treatment and to grow faster than before. (gold-essays.com)
  • T cells may be responsible for regulating the proliferation, and thus the growth, of malignant epithelial cells in BCC. (who.int)
  • A single layer of epithelial cells separates the PPs from the intestinal lumen. (prn.org)
  • Binding of the antibodies to the target cell via the Fab region, and to the effector cell Fc receptor via their Fc region would trigger ADCP, and the target cell label signal would be detected within the effector cell population. (flowmetric.com)
  • Natural killer cells (NK cells), are cells from the innate immune system that show strong cytolytic function against stressed cells such as tumoral cells and virus-infected cells. (encyclopedia.pub)
  • Among several different types of human γδ T cells, Vγ9Vδ2 is the largest subset in peripheral blood. (nature.com)
  • As detailed below, LPLs have a unique phenotype-these cells are terminally differentiated effector T cells that have pathways of stimulation that are different from peripheral blood T cells. (prn.org)
  • Neutralization: Immunoglobulins can bind to toxins or viruses, preventing them from interacting with target cells and neutralizing their harmful effects. (medicalbiochemist.com)