| 26567141 | Ovarian Carcinoma | Inhibit immunity | PD-1 Blunts the Function of Ovarian Tumor-Infiltrating Dendritic Cells by Inactivating NF-κB.
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| 25851535 | Melanoma | Inhibit immunity (T cell function) | Together, we propose that targeting the unrecognized ADAP-SKAP55-NFATc1-PD-1 pathway might increase efficacy of anti-tumor immunotherapy.
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| 25720800 | Melanoma | Inhibit immunity (T cell function) | IL10 and PD-1 Cooperate to Limit the Activity of Tumor-Specific CD8+ T Cells. Collectively, our findings offer a rationale to block both IL10 and PD-1 to strengthen the counteraction of T-cell immunosuppression and to enhance the activity of TA-specific CD8(+) T cell in advanced melanoma patients.
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| 25480946 | Head and Neck Squamous Cell Carcinoma | Inhibit immunity (T cell function) | SHP-2 activation by fusaruside suppresses p-STAT1/T-bet and production of Th1 cytokines. Overall, these results defined a PD-1/SHP-2/STAT1/T-bet signaling axis mediating the suppressive effects of PD-1 on Th1 immunity at tumor sites. Our findings argue that PD-1 or SHP-2 blockade will be sufficient to restore robust Th1 immunity and T-cell activation and thereby reverse immunosuppression in the tumor microenvironment.
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| 25387892 | Melanoma | Inhibit immunity (T cell function) | Combination of 4-1BB agonist and PD-1 antagonist promotes antitumor effector/memory CD8 T cells in a poorly immunogenic tumor model.
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| 27678219 | Melanoma | Inhibit immunity; immunotherapy target | The efficacy of the ID2-GM-DC vaccine was improved by combinatorial treatment with a blocking antibody to programmed cell death protein-1 (PD-1), a current immunotherapy that overcomes suppressive immune checkpoint signaling.
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| 27656909 | Melanoma; Breast Carcinoma | Inhibit immunity; immunotherapy target | The combinations of nanoscale MEK- and PI3K-targeting supramolecular therapeutics with checkpoint PDL1 and PD1 inhibitors exert enhanced antitumor outcome in melanoma and breast cancers in vivo, respectively.
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| 27622997 | Melanoma | Inhibit immunity (T cell function); immunotherapy target | Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Results from phase 2 and 3 trials in patients with advanced melanoma have shown significant improvements in the proportion of patients achieving an objective response and prolonged progression-free survival with the combination of nivolumab (an anti-PD-1 antibody) plus ipilimumab (an anti-CTLA-4 antibody) compared with ipilimumab alone.
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| 29378267 | Non-Small Cell Lung Carcinoma | Inhibit immunity; immunotherapy target | Safety of Combined PD-1 Pathway Inhibition and Intracranial Radiation Therapy in Non-Small Cell Lung Cancer. Treatment with an ICI and cranial RT was not associated with a significant increase in RT-related AEs, suggesting that use of programmed cell death 1/programmed death ligand 1 inhibitors in patients receiving cranial RT may have an acceptable safety profile.
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| 29351920 | Ovarian Carcinoma | Immunotherapy target | Anti-PD1 inhibitors may represent a novel treatment option for recurrent/metastatic human tumors refractory to salvage treatment harboring PD-L1 gene structural variations causing aberrant PD-L1 expression.
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| 29309059 | Metastatic Melanoma | Immunotherapy target | In particular, inhibition of programmed cell death protein 1 (PD-1) has been found to be effective for the treatment of metastatic melanoma and other cancers.
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| 29298869 | Glioma | Immunotherapy target | Finally, we show that addition of PD-1 blockade to reovirus enhances systemic therapy in a preclinical glioma model.
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| 29243219 | Bladder Carcinoma | Inhibit immunity (T cell function); immunotherapy target | PD-1 blockade enhances the antitumor efficacy of GM-CSF surface-modified bladder cancer stem cells vaccine. PD-1 blockade could effectively enhance the functions of tumor-specific T lymphocytes generated by the CSCs vaccine.
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| 24667641 | Metastatic Melanoma | Inhibit immunity (T cell function) | In all 6 tumors studied, expression of the inhibitory receptors programmed cell death 1 (PD-1; also known as CD279), lymphocyte-activation gene 3 (LAG-3; also known as CD223), and T cell immunoglobulin and mucin domain 3 (TIM-3) on CD8? TILs identified the autologous tumor-reactive repertoire, including mutated neoantigen-specific CD8? lymphocytes, whereas only a fraction of the tumor-reactive population expressed the costimulatory receptor 4-1BB (also known as CD137).
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| 24490176 | Melanoma | Immunotherapy target | Severe cutaneous and neurologic toxicity in melanoma patients during vemurafenib administration following anti-PD-1 therapy.
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| 24485523 | Melanoma | Immunotherapy target | The potential of combination strategies with these agents has recently been highlighted by clinical observations on CTLA-4+PD-1 combined blockade in melanoma patients.
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| 27865385 | Tuberculosis | Inhibit immunity (T cell function) | Decreased expression of PD-1 in Tresp and Teff cells in tuberculosis patient showed increased sensitivitiy to anti-TB therapy. Finally, clinical improvement following effective anti-TB therapy is correlated with significantly decreased expression of PD-1 in Tresp and Teff cells, but not in Treg cells.
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| 27721577 | Cervical carcinoma | Inhibit immunity | In summary, our findings demonstrate that elevated levels of PD-1/PD-L1, TGF-β, and IL-10 in peripheral blood of cervical cancer patients may negatively regulate immune response against cervical cancer cells and contribute to the progression of cervical cancer.
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| 27281199 | Adult T-Cell Leukemia; Diffuse large B-Cell Lymphoma; Gastric Adenocarcinoma | Inhibit immunity | Disruption of the Pd-l1 3'-UTR in mice enables immune evasion of EG7-OVA tumour cells with elevated Pd-l1 expression in vivo, which is effectively inhibited by Pd-1/Pd-l1 blockade, supporting the role of relevant SVs in clonal selection through immune evasion.
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| 28585539 | Colorectal Carcinoma; Melanoma; Bladder Carcinoma | Inhibit immunity (T cell function) | During this process, we find that the co-expression of Tim-3 and PD-1 marks functionally exhausted NK cells in advanced tumours and that MHC-I downregulation in tumours is closely associated with the induction of NK-cell exhaustion in both tumour-bearing mice and cancer patients.
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| 23536636 | Melanoma | Inhibit immunity (T cell function) | Concomitantly, tumor-specific CD4(+) T effector cells showed traits of chronic exhaustion, as evidenced by their high expression of the PD-1, TIM-3, 2B4, TIGIT, and LAG-3 inhibitory molecules. Although blockade of the PD-1/PD-L1 pathway with anti-PD-L1 Abs or depletion of tumor-specific regulatory T cells (Tregs) alone failed to reverse tumor recurrence, the combination of PD-L1 blockade with tumor-specific Treg depletion effectively mediated disease regression.
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| 21263073 | Colon Carcinoma | Inhibit immunity (T cell function) | IFN-α directly promotes programmed cell death-1 transcription and limits the duration of T cell-mediated immunity.
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| 27520877 | Hepatocellular Carcinoma | Inhibit immunity (T cell function); immunotherapy target | Treg accumulation and upregulation of PD-1 provide two independent mechanisms to induce profound immune tolerance in HCC. Chemoimmunotherapy using Food and Drug Administration-approved sunitinib with anti-PD-1 antibodies achieved significant tumor control, supporting translation of this approach for the treatment of HCC patients.
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| 27479178 | Chronic Lymphocytic Leukemia | Inhibit immunity; immunotherapy target | Furthermore, we report that CLL monocytes express Bruton's tyrosine kinase (BTK). Our observations suggest that using BTK inhibitors in CLL might further aggravate the observed immune metabolic defects in monocytes. Triggering the programmed cell death-1 (PD-1) checkpoint on monocytes hampers glycolysis, phagocytosis and BTK signaling. Conversely, disrupting PD-1/PD-L1 signaling reverses these immune metabolic dysfunctions. Taken together, our findings imply a novel metabolic interplay between CLL cells and monocytes and that blocking PD-1/PD-L1 might restore metabolic together with antitumor activity of CLL monocytes/macrophages.
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| 27470968 | Gastrointestinal Stromal Tumor | Inhibit immunity (T cell function) | The inhibitory receptors PD-1, lymphocyte activation gene 3, and T-cell immunoglobulin mucin-3 were upregulated on tumor-infiltrating T cells compared with T cells from matched blood. In human GIST cell lines, treatment with imatinib abrogated the IFNγ-induced upregulation of PD-L1 via STAT1 inhibition. In KitV558Δ/+?mice, imatinib downregulated IFNγ-related genes and reduced PD-L1 expression on tumor cells. PD-1 and PD-L1 blockade in vivo each had no efficacy alone but enhanced the antitumor effects of imatinib by increasing T-cell effector function in the presence of KIT and IDO inhibition.
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| 27458246 | Lymphoma; Glioblastoma | Inhibit immunity (T cell function); immunotherapy target | The injection of anti-PD-1 antibody reduced by more 50% the size of SCC-3 and U87 tumors. In addition, induction of CTLs against SCC-3 cells and upregulation of natural killer cell activity was observed in the antibody-treated group. A greater number of CD8+?and granzyme-producing T cells infiltrated the tumor in mice treated with the anti-PD-1 antibody. These results suggest that NOG-dKO mice might serve as a good humanized immunotherapy model to evaluate the efficacy of anti-PD-1 antibody prior to the clinical treatment.
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| 22466343 | Thyroid Gland Papillary Carcinoma | Inhibit immunity (T cell function) | PD-1(+) T cells were present at high frequency in TILN and markedly enriched in TILN that showed evidence of extranodal invasion. In TILN, Treg frequency correlated with PD-1(+) T cell frequencies. Although PD-1(+) T cells produced interferon-γ, they failed to fully down-regulate CD27 and were not actively proliferating.
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| 27572267 | Basal-Like Carcinoma | Inhibit immunity (T cell function) | We also demonstrate that epidermal growth factor (EGF) stabilizes PD-L1 via GSK3β inactivation in basal-like breast cancer. Inhibition of EGF signalling by gefitinib destabilizes PD-L1, enhances antitumour T-cell immunity and therapeutic efficacy of PD-1 blockade in syngeneic mouse models
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| 28424162 | Chronic Lymphocytic Leukemia; Richter Syndrome | Inhibit immunity | Preclinical studies suggest that programmed death 1 (PD-1) pathway is critical to inhibit immune surveillance in CLL.
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| 28419181 | Head and Neck Squamous Cell Carcinoma | Inhibit immunity | In the clinic, some patients seem not only not to benefit from anti-PD-L1/PD-1 agents but rather to experience an acceleration of tumor growth kinetics (TGK).Hyperprogression was observed in 29% of patients with R/M HNSCC treated with anti-PD-L1/PD-1 agents and correlated with a shorter PFS.
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| 28408386 | Head and Neck Carcinoma | Inhibit immunity (T cell function) | The frequency of PD-1 and TIM-3 expression was significantly increased in CD8+ TILs compared with CD8+ PBLs (P = 0.008 and P = 0.02, respectively). Indeed, the increased frequency of PD-1+?and TIM-3+?CD8+?TILs was inversely correlated with clinical outcome of cetuximab therapy
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| 19208793 | Melanoma; Colon Carcinoma | Inhibit immunity (T cell function) | The studies reported here show that combining PD-1 blockade with GM-CSF-secreting tumor cell immunotherapy prolonged the survival of tumor-bearing animals compared with animals treated with either therapy alone. Prolonged survival correlated with strong antigen-specific T-cell responses detected by tetramer staining and an in vivo CTL assay, higher secretion levels of proinflammatory cytokines by splenocytes, and the persistence of functional CD8+ T cells in the tumor microenvironment.
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| 29632730 | Renal Cell Carcinoma | Inhibit immunity (T cell function) | Programmed cell death protein 1 (PD-1) immune checkpoint inhibitors have shown activity in patients with advanced renal cell carcinoma (RCC).
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| 29619406 | Melanoma | Inhibit immunity (T cell function) | Programmed cell death protein 1 Monoclonal antibodies targeting two such molecules, Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) have shown clinical benefit in the treatment of advanced malignancies, including metastatic melanoma.
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| 27872087 | Renal Cell Carcinoma | Inhibit immunity (T cell function) | Inhibitory receptors expressed by T cells mediate tolerance to tumor antigens, with coexpression of these receptors exacerbating this dysfunctional state. Using the VectraR automated multiparametric immunofluorescence technique, we quantified intratumoral CD8+ T cells coexpressing the inhibitory receptors PD-1 and Tim-3 from patients with renal cell carcinoma (RCC). The percentage of tumor-infiltrating CD8+ T cells coexpressing PD-1 and Tim-3 correlated with an aggressive phenotype and a larger tumor size at diagnosis.
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| 27821498 | Head and Neck Squamous Cell Carcinoma | Inhibit immunity; immunotherapy target | These findings suggest that PD-1 pathway blockade may reverse adaptive immune resistance following cyclic dinucleotide treatment, enhancing both local and systemic antitumor immunity.
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| 27638840 | Germ Cell Tumor | Inhibit immunity; immunotherapy target | Clinical Response of a Patient to Anti-PD-1 Immunotherapy and the Immune Landscape of Testicular Germ Cell Tumors. Anti-Programed Death 1 (PD-1) is standard immunotherapy for multiple cancers, and the expression of one of its ligands, PD-L1, has been described in germ cell tumors (GCT). Neither the clinical activity of anti-PD-1 nor the incidence of an immunoresponsive tumor microenvironment has been described for GCTs. These data suggest that GCTs can respond to anti-PD-1 and that gene expression profiling supports investigation of immunotherapy for treatment of GCTs.
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| 24055012 | Melanoma | Immunotherapy target | Anti-PD1 and anti-PDL1 antibodies have emerged as breakthrough drugs for melanoma that have high response rates and long durability.
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| 24004819 | Breast Carcinoma | Inhibit immunity (T cell function) | Enhanced immune surveillance in COX-2(MEC)KO tumors was coincident with increased intratumoral CXCL9, a T cell chemoattractant, and decreased expression of T lymphocyte co-inhibitory receptors CTLA4 and PD-1, as well as PD-L1, the ligand for PD-1.
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| 23975756 | Ovarian Cancinoma | Inhibit immunity (infiltration) | The tumor microenvironment mediates induction of the immunosuppressive programmed cell death-1 (PD-1) pathway, and targeted interventions against this pathway can help restore antitumor immunity. Exhaustion of tumor-infiltrating lymphocytes (TIL) correlated with expression of PD-1 ligands by tumor cells and tumor-derived myeloid cells, including tumor-associated macrophages (TAM), dendritic cells, and myeloid-derived suppressor cells (MDSC). Overall, PD-1/PD-L1 blockade enhanced the amplitude of tumor immunity by reprogramming suppressive and stimulatory signals that yielded more powerful cancer control.
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| 23870385 | Melanoma | Inhibit immunity (T cell function) | The second major advance is the development of other immune checkpoint blocking agents, including PD-1 and PD-L1 antibodies, and the use of BRAF and MEK inhibitors in combination, with a higher proportion of durable responses coupled with less toxicity
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| 21482773 | Breast Carcinoma (ERBB-(+)) | Inhibit immunity (T cell function) | Finally, we investigated whether immunostimulatory approaches with antibodies against programmed death-1 (PD-1) or 41BB (CD137) could be used to capitalize on the immune-mediated effects of trastuzumab. We demonstrate that anti-PD-1 or anti-CD137 mAb can significantly improve the therapeutic activity of anti-ErbB-2 mAb in immunocompetent mice.
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| 21385853 | Acute Myeloid Leukemia | Inhibit immunity (T cell function) | Coexpression of Tim-3 and PD-1 identifies a CD8+ T-cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia. PD-1(+)Tim-3(+) CD8(+) T cells were deficient in their ability to produce IFN-γ, TNF-α, and IL-2 in response to PD-1 ligand (PDL1) and Tim-3 ligand (galectin-9) expressing AML cells. PD-1 knockout (KO), which were partially resistant to AML challenge, up-regulated Tim-3 during AML progression and such Tim-3(+)PD-1- KO CD8(+) T cells had reduced cytokine production. Therefore, combined PD-1/PDL1 and Tim-3/galectin-9 blockade may be beneficial in preventing CD8(+) T-cell exhaustion in patients with hematologic malignancies such as advanced AML.
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| 29360722 | Melanoma | Inhibit immunity (T cell function) | Targeting a distinct checkpoint, the PD-1 yielded improved outcomes and reduced toxicity compared with CTLA-4 blockade and, in separate studies, chemotherapy.
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| 29339209 | Esophageal Adenocarcinoma | Immunotherapy target | Importantly, PD-1-expressing T cells are significantly lower in EAC tumor post neoadjuvant chemoradiotherapy, suggesting that combination with specific conventional treatments may severely impair the efficacy of anti-PD-1 immunotherapy.
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| 29326088 | Melanoma | Immunotherapy target | We used a mouse model of transplantable, orthotopic B16 melanoma to test age effects of treatments with anti-CTLA-4, anti-PD-1 and anti-PD-L1 antibodies.
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| 29301578 | B16 Malignant Melanoma | Inhibit immunity | It could also enhance B16 cell-mediated inhibition of T cell proliferation and activation, and upregulate PD-1 expression on CD4+ and CD8+ T cells.
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| 29251665 | Lung Adenocarcinoma | Inhibit immunity (T cell function) | Therapies with antibodies that block the interaction of PD-L1 with PD-1 and thereby liberate an antitumor immune response have introduced a new era in cancer therapy with impressive therapeutic benefits.
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| 29173750 | Head and Neck Squamous Cell Carcinoma | Immunotherapy target | The application of anti-PD-1 therapies for recurrent or metastatic HNSCC has found promising results. Other ongoing trials are evaluating the use of anti-PD-1 and anti-PD-L1 therapies in the upfront setting for newly diagnosed high-risk, locally advanced HNSCC, in an effort to improve disease control.
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| 29153898 | Non-Small Cell Lung Carcinoma | Immunotherapy target | Immunotherapy targeting programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) has recently been shown to improve the survival in advanced NSCLC.
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| 18676751 | Infiltrating Bladder Urothelial Carcinoma | Inhibit immunity (T cell function) | Aberrant expression of T-cell coregulatory molecules has been investigated as a mechanism by which certain cancers may evade host immune surveillance. We evaluated expression of the T-cell coregulators B7-H1, B7-H3, and PD-1 in urothelial cell carcinoma (UCC) of the bladder.
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| 24078774 | Lung Neoplasm | Inhibit immunity | PD-1 antibody blockade improved the survival of mice with EGFR-driven adenocarcinomas by enhancing effector T-cell function and lowering the levels of tumor-promoting cytokines.
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| 22915761 | Melanoma | Inhibit immunity (T cell function) | PD-1 blockade enhances T-cell migration to tumors by elevating IFN-γ inducible chemokines. While anti-PD-1 did not reduce the number of immunosuppressive regulatory T cells and myeloid-derived suppressor cells present in tumor-bearing mice, we found that it increased expression of IFN-γ and CXCL10 at the tumor site.
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| 21551365 | Ovarian Carcinoma | Inhibit immunity | In this study, we found that ovarian cancer-infiltrating DCs progressively expressed increased levels of PD-1 over time in addition to B7-H1. These dual-positive PD-1(+) B7-H1(+) DCs have a classical DC phenotype (i.e., CD11c(+)CD11b(+)CD8(-)), but are immature, suppressive, and respond poorly to danger signals. Accumulation of PD-1(+)B7-H1(+) DCs in the tumor was associated with suppression of T cell activity and decreased infiltrating T cells in advancing tumors. T cell suppressor function of these DCs appeared to be mediated by T cell-associated PD-1.
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| 17644739 | Hodgkin Lymphoma | Inhibit immunity | RNA fingerprints provide direct evidence for the inhibitory role of TGFbeta and PD-1 on CD4+ T cells in Hodgkin lymphoma. Applying these specific fingerprints, we directly demonstrate that CD4+ T cells in HL--but not in follicular lymphoma (FL)--are under the inhibitory influence of both TGFbeta and PD-1 in vivo.
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| 23300177 | leukemia | Inhibit immunity | Within chronic lymphocytic leukemia proliferation centers in the lymph node, CD4(+)/PD-1(+) T lymphocytes were found to be in close contact with PD-L1(+) chronic lymphocytic leukemia cells. Lastly, functional experiments using recombinant soluble PD-L1 and blocking antibodies indicated that this axis contributes to the inhibition of IFN-γ production by CD8(+) T cells.
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