ReceptorDifferentiationLymphocytesTumorsExhaustionReceptorsHelper cellsPhenotypeSubsetsMicroenvironmentResponsesStimulationCytotoxicityInfiltrationPrecursorCheckpointMelanomaAntibodyImmatureInduceCytokinesBlockadeInhibitorsPathwaysInfectionMoleculesInnateCytotoxic T celViralExpressionProliferativeRegulatory T-cePersistentSurvivalPopulationsDifferentiateFoxp3PhenotypesEarly thymic progenitorMediateChronicEffector functionsImmune responseVivoAssaysImmunotherapyEpigeneticImmunitySubset2016Diseased tissuesInterestinglyMyeloidMalignant
Receptor21
- T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface. (wikipedia.org)
- The earliest cells which arrived in the thymus are commonly termed double-negative, as they express neither the CD4 nor CD8 co-receptor. (wikipedia.org)
- A critical step in T cell maturation is making a functional T cell receptor (TCR). (wikipedia.org)
- In the context of relapsed and refractory childhood pre-B cell acute lymphoblastic leukemia (R/R B-ALL), CD19-targeting chimeric antigen receptor (CAR)-T cells often induce durable remissions, which requires the persistence of CAR-T cells. (nature.com)
- In this study, we systematically analyzed CD19 CAR-T cells of 10 children with R/R B-ALL enrolled in the CARPALL trial via high-throughput single-cell gene expression and T cell receptor sequencing of infusion products and serial blood and bone marrow samples up to 5 years after infusion. (nature.com)
- The advent of CD19 chimeric antigen receptor (CAR)-T cell therapy in recent years has transformed the treatment of intractable ALL 2 . (nature.com)
- In the analyses of CD8 T cell responses, I identified previously undescribed populations of CD8 T cells that express the chemokine receptor CX3CR1 and further segregated into two populations based on expression of the inhibitory receptor TIM3. (wustl.edu)
- Consistent with an elevated susceptibility to HIV disease, PD-1 manifestation with this Compact disc4 T cell subset was connected with improved manifestation and activation from the HIV co-receptor, CCR5. (thetechnoant.info)
- Introduction PD-1 is expressed on the surface of T-cells, macrophages, and B cells and functions as an inhibitory co-receptor in the B7:CD28 family, specifically in the regulation of immune activation, inflammation and tolerance [1,2]. (thetechnoant.info)
- Most importantly, EZH2 is shown to be important for reinvigoration of exhausted chimeric-antigen-receptor (CAR)-T cells. (hmh-cdi.org)
- LAG3 is an inhibitory receptor that is highly expressed on exhausted T cells. (genengnews.com)
- Here, we show that LAG3 moved to the immunological synapse and associated with the T-cell receptor (TCR)-CD3 complex in CD4+ and CD8+ T cells, in the absence of binding to major histocompatibility complex class II-its canonical ligand. (genengnews.com)
- Now that we know LAG3 binds to the T-cell receptor, we might be able to generate optimal blockers that target this interaction," he added. (genengnews.com)
- PD-L1 is a ligand of the co-inhibitory receptor PD1 that has been shown to be expressed by tumor cells of distinct origin related to unfavorable prognosis. (biomedcentral.com)
- PD-L1 is a ligand of the co-inhibitory receptor PD1 that under physiologic conditions is constitutively expressed by activated T and B-lymphocytes, DCs, monocytes, mesenchymal stem cells, bone marrow-derived mast cells and other immune privileged organs. (biomedcentral.com)
- In this review we discuss the current knowledge in the area of peripheral immune-based biomarkers, drawing information from the results of recent clinical studies of a number of different immunotherapy modalities in the treatment of cancer, including checkpoint inhibitors, bispecific antibodies, chimeric antigen receptor T cells, and anti-cancer vaccines. (biomedcentral.com)
- Circulating tumor cells also demonstrate prognostic value as liquid biopsies in certain tumor types such as breast and prostate, with measurement of nuclear proteins such as prostate cancer androgen receptor splice variant-7, providing additional supportive information for prognosis and therapy selection [ 6 ]. (biomedcentral.com)
- TAPIR: a T-cell receptor language model for predicting rare and novel targets. (preprintclub.com)
- This wide range of receptors allows for efficient receptor mediated phagocytosis of many foreign antigens. (jscimedcentral.com)
- CTLA-4 is related to the T cell co-stimulatory receptor CD28, and acts to suppress T cell function by competing with CD28 for binding to CD80 and CD86 on antigen presenting cells and recruiting inhibitory molecules into the TCR signaling synapse. (sanguinebio.com)
- A second article in the same issue of The Journal of Experimental Medicine by Bulliard et al also explored the role of FcgR engagement on the effects of Ipilimumab as well as an agonistic antibody (DTA-1) targeting the T cell activating receptor GITR (TNFR glucocorticoid-induced TNFR-related protein), which is also expressed on both activated T cells and T REG s. (sanguinebio.com)
Differentiation20
- T cell differentiation also continues after they have left the thymus. (wikipedia.org)
- The process of differentiation then proceeds to a common lymphoid progenitor (CLP), which can only differentiate into T, B or NK cells. (wikipedia.org)
- Most of the expanded cells undergo terminally differentiation and die following antigen clearance to re-establish immune homeostasis. (wustl.edu)
- In contrast, when the pathogen persists, such as in the context of chronic viral infections or anti-tumor immunity, while T cells undergo alternative differentiation known as exhaustion due to their reduced functionality, T cells still contribute to pathogen control and its response is sustained for longer duration due to unknown mechanisms. (wustl.edu)
- These findings reveal hierarchical differentiation of exhausted CD8 T cells which transit from the previously reported TCF-1hi stem-like progenitor (TPEX) state, to T-bethi intermediate progenitor (TIM3+ CX3CR1+) state, to activated effector (TIM3+ CX3CR1+) state, which mediates sustained CD8 T cell immunity to persistent viral infection. (wustl.edu)
- Exhausted T cells are defined by the gradual loss of effector function, typically by decreased secretion of IFN-g, TNF-a, IL-2 cytokines, and terminal differentiation, and have been described in chronic viral infections in mice, rhesus macaques, and humans [3C6]. (thetechnoant.info)
- One of our pioneering research programs investigates the role of EZH2, a chromatin-modifying enzyme, which is critical for cell proliferation, differentiation, expansion, and function. (hmh-cdi.org)
- Gain-of-function EZH2 mutations in GCB cells suppress expression of genes involved in terminal differentiation and proliferation checkpoints, leading to persistent centroblast proliferation and GC hyperplasia. (hmh-cdi.org)
- EZH2 restrains development of terminal differentiation of effector CD8 T cells, promotes formation of precursor and mature memory CD8 T cells, regulates appropriate specification and identity of helper CD4 T cells, and maintains survival of differentiated antigen-specific T cells. (hmh-cdi.org)
- T cell differentiation is a tightly regulated process. (encyclopedia.pub)
- This entry briefly introduces the different stages of T cell differentiation and will discuss recent findings on the epigenetic regulation of this process. (encyclopedia.pub)
- We also discussed the epigenetic modifications associated with T cell differentiation related to cancer. (encyclopedia.pub)
- Immature SP thymocytes undergo further differentiation to generate either MHC Class II restricted CD4 SP helper or MHC Class I restricted CD8 SP cytotoxic lineage cells [ 1 ] . (encyclopedia.pub)
- Overview of T cell development and differentiation. (encyclopedia.pub)
- We also show that recombinant adenovirus vaccination induced T cell responses to the same epitopes, and led to memory T cell differentiation. (biomedcentral.com)
- Central to all these endeavors is our goal to identify 'stem-like' T and NK cells that stand at the origin of all differentiation processes underlying lasting immunological memory in the context of acute and chronic infection, malignancy and autoimmune disease. (webspaceconfig.de)
- Of note, among these influence factors, CAR T cells differentiation and exhaustion are identified as the central part due to the fact that almost all factors eventually alter the state of cells differentiation and exhaustion. (biomedcentral.com)
- The complex mechanism thought to be responsible is the interplay between Notch and Wnt, two signaling pathways playing critical roles in epithelial and mesenchymal precursor cell maintenance and differentiation. (medscape.com)
- T cells must substantially increase nutrient uptake to mount a proper immune response and failure to obtain sufficient nutrients or engage the appropriate metabolic pathways can alter or prevent effector T cell differentiation and function. (elifesciences.org)
- This review will discuss the metabolic adaptations necessary for T cells to meet changing biochemical needs throughout different stages of differentiation. (elifesciences.org)
Lymphocytes10
- Kupffer cells, hepatic stellate cells and sinusoidal endothelium) and infiltrating leukocytes (e.g., monocytes, monocyte-derived macrophages, neutrophils and lymphocytes). (mdpi.com)
- In comparison to HD, the lymphocyte percentage was slightly decreased, the percentages of CD4 and CD8 T cells in lymphocytes are similar, whereas B cell percentage increased in COVID-19 patients. (medrxiv.org)
- The Buchholz Lab investigates the development of immunological memory, starting out from single antigen-specific lymphocytes in vivo and in vitro. (webspaceconfig.de)
- In this mesenchymal subtype, a decreased number of CD8 + tumor-infiltrating lymphocytes (TILs) were detected, suggesting an association between EMT tumor cells and exclusion of these immune cells from the TME. (encyclopedia.pub)
- TIME possesses distinct populations of myeloid cells and lymphocytes to influence the immune escape of cancer, the response to immunotherapy, and the survival of patients. (biomedcentral.com)
- TIME primarily consists of myeloid cells, lymphocytes and some other innate immune cells. (biomedcentral.com)
- To circumvent this limitation, we screened mice engineered to carry eight MM lesions (NF-kappa B, KRAS, MYC, TP53, BCL2, cyclin D1, MMSET/NSD2 and c-MAF) combinatorially activated in B lymphocytes following T cell-driven immunization. (unav.edu)
- Th1 cytokines (IL-2, tumor necrosis factor, IL-12, and IFN-γ) and Th2 cytokines (IL-4, IL-5, IL-6, and IL-10) along with IL-8 and IL-17 induce antitumor activity mediated by cytotoxic T lymphocytes, natural killer cells (NK), neutrophils, and macrophages. (biomedcentral.com)
- Human derived T lymphocytes engineered to express chimeric antigen receptors, which are expanded in vitro culture and then infused into patients exerting robust cytotoxicity after tumor antigen recognition and subsequent activation. (biomedcentral.com)
- This review will discuss the metabolic changes that drive T cells into different stages of their development and how the TME imposes barriers to the metabolism and activity of tumor infiltrating lymphocytes. (elifesciences.org)
Tumors14
- To investigate the effect of hyperglycemia on anti-tumor function induced by anti-PD-1 antibody treatment, we treated STZ-induced diabetic mice with subcutaneous MC38 colon carcinoma tumors with anti-PD-1 antibody, and examined changes in tumor growth, the number of tumor-infiltrating immune cells, and the expression of chemokines and chemokine receptors. (nature.com)
- High avidity T cells (Tet hi ), if present, were only found in progressing PD-1 refractory tumors. (bmj.com)
- In response to tumors, an analogous CD4 T cell population develops in draining lymph nodes. (wustl.edu)
- PD-1 marks exhausted or suppressive T cells and can serve a pro-tumor function to help tumors evade the immune system. (ultivue.com)
- An increase in CD45RO+ T cells in tumors is associated with a better prognosis. (ultivue.com)
- While these cells show some features of exhaustion, they maintain high proliferative potential and are able to both self-renew and replenish populations of exhausted effector T cells that mediate control in chronic viral infections and tumors. (acir.org)
- Established tumors are complex, heterogeneous masses composed of malignant cells admixed with a variety of non-transformed host cells, including stromal cells, endothelial cells, and immune cells. (biomedcentral.com)
- The prevention of immune cell access into the tumor, the accumulation of inhibitory FoxP3 + regulatory T cells (Treg) and/or myeloid-derived suppressor cells (MDSCs), the activation of negative immunoregulatory pathways, and the dysregulation of effector T cells are all mechanisms by which tumors evade the host immune system. (biomedcentral.com)
- Therefore, it is not surprising that physically preventing effector CD8 + T cell infiltration or inhibiting their activity once they gain access to the tumor might be a means by which tumors protect themselves from immune attack, enabling them to persist within the host. (biomedcentral.com)
- Similarly, a genomic and proteomic analysis based on a tumor cell EMT signature conducted across almost 2000 different tumors [ 5 ] revealed a strong association between EMT and markers of inhibited or exhausted immune responses. (encyclopedia.pub)
- B16-OVA tumors benefited from a synergistic effect, reaching 75% of tumor rejection, but higher levels of exhausted T-cells in LLC-OVA tumors co-expressing PD-1, LAG3 and TIM3 precluded similar levels of efficacy. (unav.edu)
- Effective immunotherapy of stromal-rich tumors requires simultaneous targeting of cancer cells and immunosuppressive elements of the microenvironment. (aacrjournals.org)
- The imbalance of immune homeostasis in the tumor microenvironment (TME) is an essential feature of tumors, which leads to suppression of the infiltration, survival, and activation of effector cells with immune recognition and tumor-killing functions. (biomedcentral.com)
- In tumors which had high levels of infiltrating CD11b + macrophages expressing the ADCC-activating FcgRIV, T REGS were selectively depleted in an FcgR-dependant manner, while effector T cells were instead expanded. (sanguinebio.com)
Exhaustion17
- These age-related immunological changes resemble those seen during treated HIV-1 infection and include high levels of soluble inflammatory proteins, high levels of monocyte and T cell activation, T cell exhaustion and senescence, and low levels of naïve T cells ( 14 - 25 ). (frontiersin.org)
- Further insights on the roles of CD8 + specificities and TCR avidity of naturally arising tumor-specific T cells, where both high and low avidity T cells recognizing the same peptide-major histocompatibility complex (pMHC) coexist in the same tumor, are crucial for understanding T cell exhaustion and resistance to PD-1 immunotherapy. (bmj.com)
- Tet lo demonstrated precursor exhausted or progenitor T cell phenotypes marked by higher expression of Tcf-1 and T-bet, and lower expression of the exhaustion markers CD39, PD-1 and Eomes compared with Tet hi , whereas Tet hi cells were terminally exhausted. (bmj.com)
- Than exhaustion Rather, this population created even more IFN-g, MIP1-a, IL-4, IL-10, and IL-17a in comparison to PD-1low EI Compact disc4 T cells. (thetechnoant.info)
- Studies of chronic viral infection have demonstrated the importance of PD-1 in the regulation of immune exhaustion in CD8 T cells, and to a lesser extent, CD4 T cells. (thetechnoant.info)
- T cells, especially CD8 T cells, showed an enhanced expression of late activation marker CD25 and exhaustion marker PD-1. (medrxiv.org)
- T-cell exhaustion is a state of T-cell dysfunction that arises during many chronic infections and cancer. (genengnews.com)
- Our Immune exhaustion 4-plex/5-color panel enables co-localization of T cells, memory T cells, tumor cells, and the underlying PD-1 checkpoint immune exhaustion mechanism at play. (ultivue.com)
- A marker of T-cell exhaustion indicating that normal function of the cell has been disrupted. (ultivue.com)
- Next, the researchers compared how TP and TE cells acquired features of exhaustion and found that both subsets upregulated PD-1 and TOX within 3 days of both chronic and acute infection. (acir.org)
- Using multidimensional scaling analysis to cluster cells based on features of T cell exhaustion over time revealed that early (day 5) TP cells in chronic infection resembled established signatures for precursors of exhausted (day 21) T cells, while early TE cells from mice with chronic infection resembled the polyfunctional effector cells that were prominent in acute infection. (acir.org)
- When the researchers compared exhausted TP and TE cells from chronic infections against corresponding memory cells that developed after acute infection, they were able to identify a core exhaustion signature of 281 genes that included Pdcd1 , Lag3 , and Tox . (acir.org)
- This shows that in the setting of chronic infection, TP cells acquire an exhaustion signature early on. (acir.org)
- found that in chronic infection, exhaustion-related genes like Tox were highly accessible in early TP cells, mature TP cells, and mature TE cells. (acir.org)
- Single cell RNA sequencing revealed augmented signatures of activation, exhaustion, cytotoxicity, and type-I interferon signaling in memory T cells and NK cells. (medrxiv.org)
- Paiardini and his colleagues reasoned chronic viral infection and cancer produce similar states of "exhaustion": immune cells (T cells) that could fight virus or cancer are present, but unable to respond. (emoryhealthsciblog.com)
- T cell marker expression profiles showed that almost all T cells in the tumor tissue were in a state of exhaustion. (biomedcentral.com)
Receptors11
- CX3CR1+ TIM3+ cells, despite the expression of inhibitory receptors, maintain proliferative states and express effector molecules, thus contributing to antiviral responses to the persisting virus. (wustl.edu)
- When T cells engage with an antigen-presenting cell, they form a contact point called an immunological synapse that gets flooded with T-cell receptors. (genengnews.com)
- We found that LAG3 binds to T-cell receptors, but it doesn't inhibit them directly," explained Workman. (genengnews.com)
- Instead, LAG3 uses T-cell receptors to hitch a ride to the immunological synapse. (genengnews.com)
- Expressing cell surface molecules such as programmed death ligand-1 (PD-L1) and CTLA-4, tumor cells interact with the receptors on T cells mimicking the signals released by healthy cells, resulting in inactivation of immune system (Boussiotis, 2016 ). (biomedcentral.com)
- While CD4 T cells are by far the most abundant HIV-infected cell, DCs express a variety of HIV co-receptors and lectin receptors that modulate HIV uptake, antigen processing, and trans-infection to T cells, thus contributing to a wide variety of immunological outcomes. (jscimedcentral.com)
- In addition, the ability of HIV to exploit DC surface receptors or intracellular routing mechanisms to avoid antigen-processing machinery also contributes to viral persistence and promotes trans or cis-infection of CD4 T cells. (jscimedcentral.com)
- Immature DCs possess a wide variety of receptors, such as Fc receptors, lectins, and langerin, which allow them to efficiently bind and internalize antigen. (jscimedcentral.com)
- Activating receptors contain cytoplasmic immunoreceptor tyrosine-based activation motifs (ITAM) and activate the FcgR-expressing cell to mediate functions including antibody-dependant cell mediated cytotoxicity (ADCC) and phagocytosis of the antibody-labeled target cell. (sanguinebio.com)
- Thus differential affinities of IgG subclasses to functionally different Fcg receptors are thought to mediate the variation in clinical effectiveness of different antibodies targeting the same antigen. (sanguinebio.com)
- Further, inhibitory receptors present in the TME can inhibit T cell metabolism and alter T cell signaling both directly and through release of extracellular vesicles such as exosomes. (elifesciences.org)
Helper cells1
- Plasma IL-21 the signature cytokine of T follicular helper cells (Tfh) and CD4 T cell IL-21R were upregulated with seroconversion (≥4 collapse increase in antibody titer). (technuc.com)
Phenotype4
- We show that long-lived CAR-T cells developed a CD4/CD8 double-negative phenotype with an exhausted-like memory state and distinct transcriptional signature. (nature.com)
- Consistent with our earlier findings, PD-1high EI Compact disc4 T cells had been also seen as a a higher manifestation of CCR7, CXCR5 and CCR6, a phenotype associated with increased B cell help. (thetechnoant.info)
- Carcinoma cells that undergo an epithelial-mesenchymal transition (EMT) and display a predominantly mesenchymal phenotype (hereafter EMT tumor cells) are associated with immune exclusion and immune deviation in the tumor microenvironment (TME). (encyclopedia.pub)
- However, relapse of primary disease remains a major obstacle after CAR T cells therapy, and the majority of relapses present a tumor phenotype with retention of target antigen (antigen-positive relapse), which highly correlate with poor CAR T cells persistence. (biomedcentral.com)
Subsets7
- The signature was also present across T cell subsets and clonotypes, indicating that persisting CAR-T cells converge transcriptionally. (nature.com)
- ID3 - TIM3 + ) cell subsets. (acir.org)
- The clinical implications of tumor-infiltrating T cell subsets and their spatial distribution in biliary tract cancer (BTC) patients treated with gemcitabine plus cisplatin were investigated. (e-crt.org)
- In extrahepatic cholangiocarcinoma, there was a higher density of T cell subsets in the tumor core and regulatory T cells in all regions. (e-crt.org)
- The tumor margin is the major site for the active infiltration of T cell subsets with higher levels of LAG3 and TIM3 expression in BTC. (e-crt.org)
- Among the different immune subsets, T cell subsets such as cytotoxic CD8 + T cells, helper CD4 + T cells, and regulatory T cells are recognized as key components in anti-tumor immune responses [ 9 - 11 ]. (e-crt.org)
- Homeostatic, repertoire and transcriptional relationships between colon T regulatory cell subsets. (preprintclub.com)
Microenvironment8
- Fibrotic livers are characterized by an inflammatory microenvironment that is composed of various immunologically active cells, including liver-resident populations (e.g. (mdpi.com)
- This study provides fundamental insight into the functional impact of CDK4 inhibition on cells in the tumor microenvironment, which is of high importance and interest to the field. (elifesciences.org)
- A series of studies have revealed that exosomes-mediated intercellular transfer of proteins, nucleic acids, and metabolites plays a crucial role in the initiation and progression of HCC, hypoxia and angiogenesis, chemotherapy sensitivity, and cell death mode and regulates the immune microenvironment. (hindawi.com)
- Among the components of TME, distinct populations of innate and adaptive immune cells consist of tumor immune microenvironment (TIME). (biomedcentral.com)
- This single-cell analysis of clinical samples expands our insights into the immune microenvironment of urothelial carcinoma and reveals potential biomarkers and targets for immunotherapy development. (biomedcentral.com)
- Ipilimumab functions to increase the ratio of effector T cells to T REGS in the tumor microenvironment and has been shown to require binding to both types of T cells for maximal anti-tumor effectiveness. (sanguinebio.com)
- In particular, Guadecitabine greatly enhanced the efficacy of combined ICBs by increasing effector memory CD8+ T cells, inducing effector NK cells in the spleen and reducing tumor infiltrating regulatory T cells and myeloid derived suppressor cells (MDSC), in the tumor microenvironment (TME). (biomedcentral.com)
- As T cell metabolism dictates effector function, it is now apparent that the effect of cancer cell metabolism on the tumor microenvironment (TME) may impair anti-tumor immunity, and these new hallmarks of cancer are therefore inextricably linked. (elifesciences.org)
Responses17
- CAT CAR-T cells showed greater cytotoxicity and proliferative responses in vitro and maintained long-lived molecular remissions in children with relapsed or refractory ALL, as demonstrated in the CARPALL study 3 . (nature.com)
- Conclusions Targeting subdominant T cell responses with lower avidity against pMHC affinity neoepitopes showed potential for improving PD-1 immunotherapy. (bmj.com)
- In studies of CD4 T cell responses, I demonstrated that in addition to the differentiated TH1 and follicular helper (Tfh) cells, activated CD4 T cells also differentiate into memory-like cells in a BCL6-dependent manner. (wustl.edu)
- While the initial TH1 cells and Tfh cells are generated through independent developmental pathways directly from naïve T cells, as infection persists, TH1 cells and Tfh cells are both generated from this newly identified memory-like cells, which is required to maintain both TH1 and Tfh responses for prolonged duration. (wustl.edu)
- Tregs, which comprise a separate CD4 lineage, work to prevent autoimmune diseases through suppressing the immune system's responses to self-antigens [ 5 ] . (encyclopedia.pub)
- Meanwhile, among 8 CD4 + T cell clusters, three were Th1/Th17-like clusters, which were not associated with antitumor responses. (acir.org)
- There were also two CD4 + regulatory T cell (T reg ) clusters, of which one (ICOS - CD62L + ) had an inverse correlation with antitumor responses. (acir.org)
- CD45RO is a marker for memory T cells, which have been primed against antigens and can provide anti-tumor immune responses. (ultivue.com)
- While the T cell precursor subset is known to play an important role in T cell responses, little is known about how or when these cells arise. (acir.org)
- In the past, this unique experimental approach of "single-cell fate-mapping" has shown us that even physiological immune responses to infection do not harness the full protective potential available in every antigen-specific lymphocyte. (webspaceconfig.de)
- To enhance vaccine potency and improve thus responses to ICI, we analyzed the gene expression profile of an immunosuppressive dendritic cell (DC) population induced during vaccination, with the goal of identifying druggable inhibitory mechanisms. (unav.edu)
- Gene expression signatures within memory B cells suggest qualitative differences in the antibody responses in aged patients with severe disease. (medrxiv.org)
- Dendritic cells (DC) are central purveyors of both innate and adaptive immune responses. (jscimedcentral.com)
- A failure of DCs to mature, as witnessed during HIV uptake, however, leads to attenuation of antigen-specific immune responses and may significantly contribute to induction of T cell regulatory responses. (jscimedcentral.com)
- The failure of DCs to properly process and present HIV antigens and stimulate specific adaptive responses can prevent viral clearance and aid in establishment of viral reservoirs, two of the main obstacles to a therapeutic cure. (jscimedcentral.com)
- They are also key players in spread of infection via trans-CD4 T cell infection (or in cis), and stimulation of adaptive immune responses in attempt to eliminate virus. (jscimedcentral.com)
- This review focuses on how HIV is recognized and processed by DCs, the responses (and lack thereof) generated by DCs after capture, the role of DCs in HIV transfer to CD4 T cells, and the role of DCs in immunomodulatory responses to HIV. (jscimedcentral.com)
Stimulation2
- The T cell immune phenotypic profile in blood donors was related to loss of T cell function, whereas the same set of markers were related to chronic antigen stimulation and immune senescence in HIV-negative individuals. (frontiersin.org)
- Meanwhile, in early TP cells, there was a strong enrichment for DNA binding motifs of TCF1, JUN, AP-1, and NFAT family transcription factors, which are commonly activated in response to TCR stimulation. (acir.org)
Cytotoxicity2
- Polyclonal CD4 + and CD8 + T eff had increased expression of activation (PD-1, Tim-3, Lag-3, ICOS), survival (Bcl-2), and cytotoxicity markers (granzyme B, IFNγ, TNFα, T-bet). (acir.org)
- In ICB-refractory MM models, increasing CD8(+) T cell cytotoxicity or depleting T-reg cells reversed immunotherapy resistance and yielded prolonged MM control. (unav.edu)
Infiltration4
- These results suggest that the STZ-induced hyperglycemia impairs the effect of PD-1-Ab treatment on MC38 tumor growth, and is accompanied by reduced infiltration of DCs and CD8 + T cells and decreased expression of CCL7 and CXCL9. (nature.com)
- In a study of lung adenocarcinoma [ 4 ] , EMT markers were associated with enhanced tumor infiltration of CD4 + Foxp3 + Tregs and upregulation of inhibitory immune checkpoint molecules such as programmed cell death (PD)-ligand (L) 1, PD-L2, TIM-3, B7-H3, and CTLA-4. (encyclopedia.pub)
- Rapid MYC-driven progressors exhibited a high number of activated/exhausted CD8(+) T cells with reduced immunosuppressive regulatory T (T-reg) cells, while late MYC acquisition in slow progressors was associated with lower CD8(+) T cell infiltration and more abundant T-reg cells. (unav.edu)
- This improved efficacy was associated with higher tumor T-cell infiltration and overexpression of PD-1/PD-L1. (unav.edu)
Precursor1
- After migration to the thymus, the precursor cells mature into several distinct types of T cells. (wikipedia.org)
Checkpoint7
- Immune checkpoint inhibitors (ICIs), including antibodies against programmed cell death-1 (PD-1) and PD-1 ligand-1 (PD-L1), induce their anti-tumor effects by improving the function of immune cells 11 . (nature.com)
- One immunotherapy that revitalizes T cells by blocking an immune checkpoint protein called LAG3 was recently approved by federal regulators. (genengnews.com)
- Single-cell transcriptomics and functional assays defined a high ratio of CD8(+) T cells versus T-reg cells as a predictor of response to immune checkpoint blockade (ICB). (unav.edu)
- Recently, the analysis of TMB and T-cell gene expression provided value in identifying patients most likely to respond to pembrolizumab, suggesting the potential value for these biomarkers in the selection of patients for checkpoint therapy [ 5 ]. (biomedcentral.com)
- In long-term HIV or SIV infection, T cells harboring the virus display molecules on the cell surface that make them targets for checkpoint inhibitors, cancer immunotherapy drugs that are designed to counteract the exhausted state. (emoryhealthsciblog.com)
- Pre-requisite of tumor response to ICBs is the co-expression by cancer cells of immunogenic tumor antigens and targetable immune checkpoint molecules. (biomedcentral.com)
- Two of the primary immunotherapies are immune checkpoint blockade (ICB) and adoptive cell transfer (ACT). (elifesciences.org)
Melanoma3
- There was also an increase in the number of CD8 + T eff specific to B16 melanoma antigens (p15 and TRP-2). (acir.org)
- PD-L1 are expressed on the cell surface of numerous cancers, including bladder, melanoma, renal cell carcinoma, lung cancer and ovarian cancer characterizing an important step toward cancer progression (Wang et al. (biomedcentral.com)
- The combination of Programmed Cell Death 1 (PD-1) and Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) blockade has dramatically improved the overall survival rate for malignant melanoma. (biomedcentral.com)
Antibody12
- however, it remains unknown whether the anti-tumor effects of anti-programmed cell death-1 antibody (PD-1-Ab) treatment are changed in hyperglycemic conditions. (nature.com)
- Mice were intraperitoneally injected with STZ or sodium citrate buffer (CB) 7 days before subcutaneous inoculation with MC38 cells in the right flank on day 0 (Fig. 1 A). Then, the mice were treated with anti-PD-1 antibody or normal rat IgG on days 5, 8, and 11. (nature.com)
- A test is defined as the amount (µg) of antibody that will stain a cell sample in a final volume of 100 µL. (thermofisher.com)
- The PD-1 FixVUE antibody panel enables users to profile tumor samples by detecting the location and abundance of memory T cells and exhausted T cells. (ultivue.com)
- Post-vaccine antibody reactions were inversely correlated with pre-vaccination plasma TNFα levels and with triggered CD4 T cells including triggered peripheral (p)Tfh. (technuc.com)
- Higher frequencies of triggered and exhausted CD8 T and B cells were mentioned in HIV+ ladies but these markers did not show a correlation with antibody reactions. (technuc.com)
- Conclusions In ageing HIV-infected and uninfected ladies activated CD4 and pTfh cells may compromise influenza Malol vaccine-induced antibody response for which a mechanism of TNFα-mediated impairment of pTfh-induced IL-21 secretion is definitely postulated. (technuc.com)
- The pTfh cells represent approximately 15% of circulating CD4 T cells in humans [27] communicate CXCR5 and provide critical help to B cells for antibody secretion in an IL-21-dependent manner [26]. (technuc.com)
- The pTfh cells represent around 15% of circulating Compact disc4 T cells in human beings [27] communicate CXCR5 and offer critical help B cells for antibody secretion within an IL-21-reliant way [26]. (healthdisparitiesks.org)
- Reasons may include the different sources of EBV antigens, different antibody assays and the selection of cases from different geographic origins. (labriegorural.es)
- ScFv is the antigen-binding domain of CAR structure, which is composed of a single heavy and light chain of monoclonal antibody connected by a linker. (biomedcentral.com)
- Even though GITR-activation in effector T cells promotes activities including cytokine production and proliferation, the agonistic properties of this antibody alone were not effective in the absence of activating FcgR engagement. (sanguinebio.com)
Immature3
- Henceforth they are known as thymocytes, the immature stage of a T cell. (wikipedia.org)
- B-lineage acute lymphoblastic leukemia (B-ALL) is the most common type of childhood cancer and mostly derives from immature B cells that carry the cell surface antigen CD19 (ref. 1 ). (nature.com)
- Most DCs in tissues and blood are present in an immature state, but upon antigen acquisition and activation they mature. (jscimedcentral.com)
Induce4
- To induce hyperglycemia, mice were intraperitoneally injected with STZ, which can damage pancreatic β cells resulting in the development of insulin dependent diabetes, a model of type 1 diabetes mellitus (T1DM). (nature.com)
- Through direct interaction with WDR1, GA-amide promoted the formation of a complex involving WDR1, MYH9 and Cofilin, which accelerate the depolymerization of F-actin to inhibit the invasion of patient-derived glioma cells (PDCs) and induce PDC apoptosis via the mitochondrial apoptotic pathway. (bvsalud.org)
- Little is known of the T cell repertoire these recombinant vaccines induce. (biomedcentral.com)
- IL-10, TGF-β, chronic infection and cancer induce PD1 expression by different cytokines and is a characteristic of exhausted T cells (Wherry & Kurachi, 2015 ). (biomedcentral.com)
Cytokines7
- CD8+ T cells are also able to use small signalling proteins, known as cytokines, to recruit other types of cells when mounting an immune response. (wikipedia.org)
- The specific adaptive immune response regulated by the TH cell depends on its subtype (such as T-helper1, T-helper2, T-helper17, regulatory T-cell), which is distinguished by the types of cytokines they secrete. (wikipedia.org)
- Different T cells secrete various cytokines to exert their activity. (encyclopedia.pub)
- Signature transcription factors and cytokines designated to different cell types are shown. (encyclopedia.pub)
- CTLs) that produce cytokines and cytotoxic enzymes (perforin, granzyme B) that eliminate pathogens or target cells (including pathogen-infected host cells and tumor cells) and can develop into memory T cells ( Figure 1 ) [ 12 ] . (encyclopedia.pub)
- For evaluation of peripheral immune-cell function, several immune-related analytes may be measured, including cytokines, soluble plasma proteins, and immune cells, analyzed by surface marker expression, transcriptomic, or epigenetic profiles. (biomedcentral.com)
- Examination of T cells showed profound lymphopenia, that worsened over time and correlated with lower levels of plasma cytokines important for T cell survival in aged patients with severe disease. (medrxiv.org)
Blockade3
- The addition of IL-6 blockade resulted in an increase of CD44 hi CD11a hi CD8 + and CD4 + effector T cells (T eff ) induced by anti-CTLA-4. (acir.org)
- In vitro TNFα blockade improved the ability of CD4 T cells to produce IL-21 and of B cells to secrete immunoglobulins and addition of exogenous IL-21 to cell cultures enhanced B cell function. (technuc.com)
- In monkeys that received both CTLA-4- and PD-1-blocking agents, researchers observed a stronger activation of T cells, compared to only PD-1 blockade. (emoryhealthsciblog.com)
Inhibitors1
- Interestingly, P-Tex cells expressed CDK4 genes as high as cancer cells, which could be simultaneously inhibited by CDK4 inhibitors and might be a potential reason for the ineffectiveness of CDK4 inhibitors in treating HPV-positive HNSCC. (elifesciences.org)
Pathways2
- P-Tex cells could aggregate in the antigen-presenting cell niches and activate certain signaling pathways. (elifesciences.org)
- We will also shortly discuss how leveraging single cell multi-omic approaches can be used to accelerate cellular biomarker discovery during clinical trials to predict response to therapy, follow responsive cell types, and define novel druggable target pathways. (frontiersin.org)
Infection13
- The main model used is the mouse chronic lymphocytic choriomeningitis virus (LCMV-clone 13, c13) infection model, which causes viremia that lasts 3-4 months in immunocompetent mice and is subsequently resolved in a manner dependent on CD4 and CD8 T cells. (wustl.edu)
- TIFF) pone.0144767.s002.tiff (4.8M) GUID:?4D6AB169-CCC8-4594-81E5-1BFE8E91C136 S3 Fig: (A) Sorted memory (Early/Intermediate, CD27high Polydatin (Piceid) CD45RAhigh) CD4 T cells from two healthy donors were subjected in vitro HIV infection. (thetechnoant.info)
- Our data show that expression of PD-1 on early-differentiated CD4 T cells may represent a population that is highly functional, more susceptible to HIV infection and selectively lost in chronic HIV infection. (thetechnoant.info)
- this was found to be the direct result of higher viral loads, and thus higher antigen burden in the chronic infection model. (acir.org)
- However, only in chronic infection did TOX and PD-1 expression continue to increase with ongoing cell divisions in both TP and TE cells. (acir.org)
- TP cells expressed higher levels of TOX and lower levels of IFNγ compared to their TE counterparts, and production of IFNγ by TPs was lower in chronic infection compared to acute. (acir.org)
- Next, the researchers performed RNAseq on TP and TE cells at different time points post-infection and found that large numbers of genes were differentially expressed between early TP and early TE cells in both chronic and acute infection. (acir.org)
- In chronic infection, the difference between TP and TE cells became more pronounced over time, while in acute infection, the difference between the two subtypes became less pronounced as the infection resolved, in line with both subtypes transitioning into resting memory T cells. (acir.org)
- Further analysis revealed that early TP cells were highly enriched for genes commonly upregulated in exhausted T cells, while TP cells from acute infection were enriched for genes commonly upregulated in polyfunctional cells. (acir.org)
- TP cells were also enriched for binding motifs for BACH2, which limits TCR-induced transcriptional changes and promotes the development of memory phenotypes in acute infection. (acir.org)
- showed that P14 T cells lacking BACH2 failed to generate TP cell populations in mice with chronic LCMV infection, while overexpression of BACH2 enforced TP cell generation. (acir.org)
- The HIV/AIDS pandemic in the 1980s then gave a dramatic impulse to the technology of counting specific cells, since it became clear that the quantification of peripheral blood CD4+ T cells was crucial to follow the course of the infection, and eventually for monitoring response to therapy ( 2 ). (frontiersin.org)
- Dendritic cells (DC) are both widely dispersed in the body and are potent activators of effector immune response, which stresses their important role in HIV infection [1,2]. (jscimedcentral.com)
Molecules3
- Isolation of multiple types of molecules (DNA, RNA, or protein) from a single cell simultaneously, stands at the beginning of each approach and having standardized and validated protocols for single cell solutions is surely the foundation of all the herein described approaches. (frontiersin.org)
- TME consists of cell component, the extracellular matrix (ECM) and abundant soluble signaling molecules. (biomedcentral.com)
- Urothelial and bladder tumor cells infected by BCG increases the expression of antigen-presenting molecules, inducing immune response via cytokine release. (biomedcentral.com)
Innate2
- and the innate immune cells contain natural killer (NK) cells and dendritic cells (DCs) (Fig. 1 ). (biomedcentral.com)
- Memory Th1 cells modulate heterologous diseases through innate function. (preprintclub.com)
Cytotoxic T cel1
- Unlike CD8+ killer T cells, the CD4+ helper T (TH) cells function by further activating memory B cells and cytotoxic T cells, which leads to a larger immune response. (wikipedia.org)
Viral5
- Right here, we explain the differential manifestation of PD-1 in Compact disc127high Compact disc4 T cells inside the early/intermediate differentiated (EI) (Compact disc27highCD45RAlow) T cell human population among uninfected and HIV-infected topics, with higher manifestation associated with reduced viral replication (HIV-1 viral fill). (thetechnoant.info)
- Stimulating immune cells with two cancer immunotherapies together can shrink the size of the viral "reservoir" in SIV (simian immunodeficiency virus)-infected nonhuman primates treated with antiviral drugs, Emory researchers and their colleagues have concluded. (emoryhealthsciblog.com)
- Additionally, researchers quantified the frequency of CD4 cells, the main reservoir of HIV and SIV, harboring intact viral DNA capable of replicating. (emoryhealthsciblog.com)
- We believe this is due to having much less viral antigens around after long-term antiretroviral therapy, compared with the situation in cancer," says Justin Harper, lab manager and first author of the paper. (emoryhealthsciblog.com)
- HIV uptake by DCs is unique in that it does not preferentially drive DC maturation and stimulate T cell instruction, but rather favors viral spread [10]. (jscimedcentral.com)
Expression9
- Expression of both CD4 and CD8 makes them double positive, and matures into either CD4+ or CD8+ cells. (wikipedia.org)
- Furthermore, we assessed the expression of chemokines by polymerase chain reaction (PCR) array in tumor-draining lymph nodes (dLNs) of these mice and MC38 cells cultured in different glucose concentrations. (nature.com)
- mRNA expression levels of CXCL9, a chemokine recruiting CD8 + T cells, were lower in dLNs of STZ-mice than in normoglycemic mice after PD-1-Ab treatment, and its protein was expressed in DCs. (nature.com)
- In MC38 cells cultured with 25 mM glucose, mRNA expression of CCL7, a chemokine recruiting DCs, was decreased compared to cells cultured with 5 mM glucose. (nature.com)
- Naïve human CD4 + T cells, which are now considered to be a heterogeneous population, can be subcategorized based on CD31 (also known as PECAM1) expression, into the youngest (recent thymus emigrant) naïve T cells (CD31 + ) and more established "mature" naïve T cells (CD31 − ) [ 2 ] [ 3 ] . (encyclopedia.pub)
- Cell scores calculated based on the gene expression profiles revealed that the cell expression gene scores for Th17, Th1, and neutrophils were upregulated in irEC. (acir.org)
- We analyzed the expression of PD1 and PD-L1 using qRT-PCR in RT4 bladder cancer (BCa) epithelial cells co-cultivated with peripheral blood mononuclear cells (PBMC) after treatment with BCG. (biomedcentral.com)
- There was a significantly reduction in PD1 and PD-L1 expression by BCa epithelial cells after BCG treatment. (biomedcentral.com)
- Tumor-associated T REGS expressedhigher levels of CTLA-4 than their effector T cell counterparts, or than T REGS present in the lymph node, indicating that higher CTLA-4 expression levels mediate ADCC via macrophages in the tumor. (sanguinebio.com)
Proliferative2
- A proliferative exhausted CD8 + T cell cluster (P-Tex) which was beneficial to survival outcomes of patients with HPV-positive HNSCC was identified. (elifesciences.org)
- The compelling conclusion that proliferative exhausted T cells are associated with response in HPV+ head and neck cancer is supported by the cohort of 14 patients with paired tumor and adjacent normal tissue and rigorous bioinformatic analysis of nearly 50,000 single CD3+ T cell transcriptomes. (elifesciences.org)
Regulatory T-ce1
- However, hyperglycolysis, a hallmark of TNBC cells, may drive tumor-intrinsic PD-L1 glycosylation and boost regulatory T cell function to impair ICI efficacy. (bvsalud.org)
Persistent4
- These findings raise the possibility that a universal transcriptional signature of clinically effective, persistent CD19 CAR-T cells exists. (nature.com)
- The goal of my thesis work is to understand how protective T cell response is sustained at the cellular levels and molecular levels for CD8 T cells and CD4 T cells in the presence of persistent antigens. (wustl.edu)
- These findings reveal the heterogeneity and plasticity of CD4 T cells upon encountering persistent antigen and highlights their population dynamics through a stable and bipotent intermediate state. (wustl.edu)
- Together, our findings suggest a promising role for P-Tex cells in the prognosis of patients with HPV-positive HNSCC by providing modest but persistent anti-tumor effects. (elifesciences.org)
Survival5
- Two retrospective studies from Israel 12 and Japan 13 recently reported that diabetes was negatively correlated to overall survival in patients with non-small cell lung cancer (NSCLC) treated with ICIs. (nature.com)
- The survival prognosis of human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) is largely different, and little is known about the anti-tumor mechanism of tumor-infiltrated exhausted CD8 + T cells (Tex) in HNSCC. (elifesciences.org)
- Depletion of NK cells improved the rate of cardiac allograft 63 acceptance and extended the survival of corneal allografts 64, while functional NK cells were found to assist the CD4 mediated allograft rejection 65. (labriegorural.es)
- A high density of FoxP3 − CD4 + helper T cells in the tumor margin showed a trend toward better progression-free survival (PFS) (p=0.092) and significantly better overall survival (OS) (p=0.012). (e-crt.org)
- Therefore, study on factors and mechanisms that limit the in vivo persistence of CAR T cells is crucial for developing strategies to reduce the probability of tumor relapse and improve the long-term disease-free survival for patients who are treated with CAR T cells. (biomedcentral.com)
Populations4
- Rabbit Polyclonal to CDH23 (B) Gating technique for sorting PD-1highCD127high Early/Intermediate along with other Compact Polydatin (Piceid) disc4 T cell populations. (thetechnoant.info)
- D) Consultant movement cytometry, gating technique and overlay plots after polyclonal excitement with SEB for IFN-g or IL-17 (demonstrated) producing Compact disc4 T-cells for particular populations is demonstrated. (thetechnoant.info)
- Here we collected the blood samples from 18 healthy donors (HD) and 38 COVID-19 patients to analyze changes in the adaptive immune cell populations and phenotypes. (medrxiv.org)
- Thus, even for functionally different (antagonistic versus agonistic) immunotherapeutic antibodies targeting these same T cell populations, FcgR-mediated ADCC of T REG s appears to be a critical mechanism for anti-tumor effects. (sanguinebio.com)
Differentiate3
- The HSC then differentiate into multipotent progenitors (MPP) which retain the potential to become both myeloid and lymphoid cells. (wikipedia.org)
- In response to transient antigen presence in the context of acute infections or vaccinations, antigen-specific naïve T cells clonally expand and differentiate. (wustl.edu)
- After encountering antigen, naïve CD4 + T cells differentiate into CD4 + effector T cells, which can take the form of well-defined subgroups that express distinct cytokine profiles: T helper 1 (Th-1), Th-2, Th-9, T follicular helper (Tfh) cells, and Th-17 cells ( Figure 1 ) [ 4 ] . (encyclopedia.pub)
Foxp35
- These cells express the master regulator transcription factor (TFs) Foxp3. (encyclopedia.pub)
- The density of CD8 + T cells, FoxP3 − CD4 + helper T cells, and FoxP3 + CD4 + regulatory T cells was significantly higher in the tumor margin than in the stroma and tumor core. (e-crt.org)
- The density of LAG3 - or TIM3-expressing CD8 + T cell and FoxP3 − CD4 + helper T cell infiltrates was also higher in the tumor margin. (e-crt.org)
- In multivariate analyses, a high density of FoxP3 − CD4 + helper T cells in the tumor margin was independently associated with favorable PFS and OS. (e-crt.org)
- The density of tumor margin-infiltrating FoxP3 − CD4 + helper T cells may be associated with clinical outcomes in BTC patients treated with gemcitabine plus cisplatin. (e-crt.org)
Phenotypes3
- In this review we will discuss how combinations and fusions of different -omic workflows on a single cell level can be used to examine cellular phenotypes, immune effector functions, and even dynamic changes, such as metabolomic state of different cells in a sample or even in a defined tissue location. (frontiersin.org)
- An association between EMT tumor cells (mesenchymal and hybrid epithelial-mesenchymal phenotypes) and increased numbers of infiltrating PD-1 + cells was also observed in another study in patients with adenocarcinoma of the lung [ 6 ] . (encyclopedia.pub)
- Among the large number of cells assayed, we identified 71 T-cell phenotypes, 30 tumor-associated macrophage phenotypes. (biomedcentral.com)
Early thymic progenitor1
- The newly arrived CLP cells are CD4−CD8−CD44+CD25−ckit+ cells, and are termed early thymic progenitor (ETP) cells. (wikipedia.org)
Mediate1
- Exosomes act as a signal-transmitting medium between cells to mediate intercellular communication and change the functional status of recipient cells [ 11 ]. (hindawi.com)
Chronic4
- We observed that age advancement in all three groups combined was associated with a monocyte immune phenotypic profile related to inflammation and a T cell immune phenotypic associated with immune senescence and chronic antigen exposure. (frontiersin.org)
- The identified monocyte and T cell immune phenotypic profiles that were associated with age advancement, were strongly related to inflammation, chronic antigen exposure and immune senescence. (frontiersin.org)
- This persistence signature was also detected in two adult patients with chronic lymphocytic leukemia with decade-long remissions who received a different CD19 CAR-T cell product. (nature.com)
- An exception was long-lived CAR-T cells in two adult individuals with a different cancer-chronic lymphocytic leukemia (CLL)-in whom anti-CD19 CAR-T cells have persisted for almost a decade thus far 7 . (nature.com)
Effector functions3
- Another type of T cell with limited effector functions is known as the exhausted T cell (T ex ). (encyclopedia.pub)
- Decreasing the dose of the virus increased IFNγ production by TP cells, suggesting that higher antigen loads led to the generation of TP cells with repressed effector functions. (acir.org)
- Iron is critical for mucosal-associated invariant T cell metabolism and effector functions. (preprintclub.com)
Immune response5
- T cells are one of the important types of white blood cells of the immune system and play a central role in the adaptive immune response. (wikipedia.org)
- Groups of specific, differentiated T cell subtypes have a variety of important functions in controlling and shaping the immune response. (wikipedia.org)
- These same regulatory T cells can also be co-opted by cancer cells to prevent the recognition of, and an immune response against, tumor cells. (wikipedia.org)
- Memory T cells (which are generated from activated CD4 + and CD8 + T cells) persevere following the generation of a primary immune response and are able to mount an enhanced secondary response to the same antigen [ 12 ] . (encyclopedia.pub)
- Determine whether the immune response has exhausted. (ultivue.com)
Vivo4
- Therefore, study on factors and mechanisms that limit the in vivo persistence of CAR T cells is crucial for developing strategies to overcome these limitations. (biomedcentral.com)
- In this review, we summarize the rapidly developing knowledge regarding the factors that influence CAR T cells in vivo persistence and the underlying mechanisms. (biomedcentral.com)
- Various factors in the process contribute to impact the in vivo persistence and durable antitumor effects of CAR T cells. (biomedcentral.com)
- In contrast, ACT expands a patient's own T cells ex vivo to direct anti-tumor immunity when transfused back into the patient. (elifesciences.org)
Assays3
- We reasoned that single-cell transcriptomic assays may help elucidate these features. (nature.com)
- Tetramer staining was performed to determine the frequency and avidity of CD8 + T cells targeting the tumor-specific epitope GSW11 and confirmed with tetramer competition assays. (bmj.com)
- Highly specific tests, such as enzyme-linked immunosorbent assays ELISA typically involve chromophore reporters that produce a color, fluorescent, or electro-chemiluminescent change to indicate the presence of specific antigen 10. (labriegorural.es)
Immunotherapy3
- Background CD8 + T cells are a highly diverse population of cells with distinct phenotypic functions that can influence immunotherapy outcomes. (bmj.com)
- Expanded understanding of the basic biology of T cell activation has enabled immunotherapy to combat cancer, and T cell metabolism now offers the opportunity to optimize and improve these therapeutic strategies. (elifesciences.org)
- Finally, we will provide an overview of how utilizing an understanding of T cell metabolism may inform strategies to alter the TME or enhance T cell metabolism to strengthen the immunotherapy arsenal. (elifesciences.org)
Epigenetic2
- Recent work suggest that epigenetics changes observed in myeloma cells are critical for response or resistance to therapy, and drugs that alter epigenetic marks on the DNA are being pursued. (hmh-cdi.org)
- Several approaches to overcome resistance to ICBs are being investigated among which the addition of epigenetic drugs that are expected to act on both immune and tumor cells. (biomedcentral.com)
Immunity2
- In a recent study, our research team discovered that EZH2 plays a central role in regulating T cell immunity against tumor. (hmh-cdi.org)
- Led by our esteemed experts, the members of iMML are passionately committed to advancing our understanding of EZH2 regulation of T cell immunity for innovative therapies by identifying and exploring novel targets such as EZH2. (hmh-cdi.org)
Subset2
- Although a subset of children can be cured, up to 60% of children experience further, typically fatal, disease recurrence due to non-persistence of CAR-T cells or CD19 − leukemic escape 3 , 4 . (nature.com)
- In past studies, researchers have identified a subset of T cells that serve as precursors to exhausted T cells. (acir.org)
20161
- 2016 ). Based on this immune deregulation by tumor cells, new target drugs were developed inhibiting PD-L1 (atezolizumab, durvalumab, avelumab, and BMS-936559) and PD1 (nivolumab and pembrolizumab) opening a new perspective for urothelial carcinoma treatment (Bellmunt et al. (biomedcentral.com)
Diseased tissues1
- Examination of single T cell transcriptomes from a wide range of healthy and diseased tissues across children and adults indicated that the persistence signature may be specific to long-lived CAR-T cells. (nature.com)
Interestingly1
- Interestingly, a unique monocyte and T cell immune phenotypic profile predictive for age advancement was found within each group. (frontiersin.org)
Myeloid2
- Although hallmarks of a cytokine storm were evident in both groups, older individuals exhibited elevated levels of chemokines that mobilize inflammatory myeloid cells, notably in those who succumbed to disease. (medrxiv.org)
- Several of these critical changes, such as the reduction of surface HLA-DR on myeloid cells, were reversed in young but not aged patients over time. (medrxiv.org)
Malignant3
- This elaborate web of diverse cell types fosters malignant tumor cell interactions with the tumor associated vasculature and fibroblasts as well as a variety of immune cells in support of tumor growth, invasion, and metastasis. (biomedcentral.com)
- Cancer is not a chaotic malignant cell mass, but a delicate "hostile" organ, where many other cells are recruited and domesticated to become "accomplices", thereby protecting themselves from recognition and attack by the immune system [ 1 ]. (biomedcentral.com)
- Conversely, malignant cells evolve mechanisms that allow them to evade immune recognition. (biomedcentral.com)