| 28274999 | Gastric Carcinoma | Inhibit immunity | Our results illuminate a novel mechanism of PD-L1 expression on tumour-activated neutrophils in GC, and also provide functional evidence for these novel GM-CSF-PD-L1 pathways to prevent, and to treat this immune tolerance feature of GC.
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| 26762740 | Non-Small Cell Lung Carcinoma | Inhibit immunity (T cell function) | PD-L1 Is Upregulated by Simultaneous Amplification of?the PD-L1 and JAK2 Genes in Non-Small Cell Lung?Cancer.
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| 26564005 | Follicular Dendritic Cell Sarcoma | Inhibit immunity (T cell function) | Last, focal copy-number gain of chromosome 9p24 including the genes CD274 (PD-L1) and PDCD1LG2 (PD-L2) was noted in three cases, which represents a well-described mechanism of immune evasion in cancer.
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| 26966191 | Leukemia; Lymphoma | Inhibit immunity (T cell function) | MYC inactivation in mouse tumors down-regulated CD47 and PD-L1 expression and enhanced the antitumor immune response.
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| 26408403 | Laryngeal Squamous Cell Carcinoma | Inhibit immunity (T cell function) | Increased TILs density and PD-L1 levels are associated with better outcome in laryngeal squamous cell cancer. Assessment of TILs and PD-L1 expression could be useful to predict response to immune checkpoint inhibitors.
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| 25943534 | Colorectal Carcinoma | Inhibit immunity (T cell function) | Taken together, our results demonstrate that inhibition of PD-L1 function can have potent antitumor activity when used as monotherapy or in combination in preclinical models, and suggest it may be a promising therapeutic approach for the treatment of cancer.
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| 25597412 | Non-Small Cell Lung Carcinoma | Inhibit immunity (T cell function) | Our discoveries suggest that the miR-197/CKS1B/STAT3-mediated network can drive tumor PD-L1 expression as a biomarker of this cascade, and miR-197 replacement therapy may be a potential treatment strategy for chemoresistant NSCLC.
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| 25428504 | Melanoma | Inhibit immunity (T cell function) | Together, these data suggest that MPDL3280A is most effective in patients in which pre-existing immunity is suppressed by PD-L1, and is re-invigorated on antibody treatment.
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| 25348003 | Lung Carcinoma | Inhibit immunity (T cell function) | We show that microRNA-200 (miR-200), a cell-autonomous suppressor of EMT and metastasis, targets PD-L1. Moreover, ZEB1, an EMT activator and transcriptional repressor of miR-200, relieves miR-200 repression of PD-L1 on tumour cells, leading to CD8(+) T-cell immunosuppression and metastasis.
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| 22547582 | Chronic Lymphocytic Leukemia | Inhibit immunity | In the present study, we show via functional screening assays that CD200, CD270, CD274, and CD276 are coopted by CLL cells to induce impaired actin synapse formation in both allogeneic and autologous T cells.
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| 29361135 | Non-Small Cell Lung Carcinoma | Inhibit immunity | Expression of PD-L1 in tumor cells and tumor-infiltrating immune cells has been associated with improved efficacy to anti-PD-1/PD-L1 inhibitors in patients with advanced-stage non-small-cell lung cancer (NSCLC) and emerged as a potential biomarker for the selection of patients to cancer immunotherapies.
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| 27568346 | Lung adenocarcinoma | Inhibit immunity | PD-L1 expression was associated with abundant CD8+ and/or T-bet+ tumor-infiltrating lymphocytes and EGFR wild-type, significant smoking history, and aggressive pathologic features. PD-L1 expression was significantly associated with decreased progression-free and overall survival rates by univariate analysis, but not by multivariate analysis.
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| 27697578 | Penile Carcinoma | Inhibit immunity | Compared to PD-L1 negative tumors, the PD-L1 expression patterns had different prognostic values in the whole cohort as well as in the high risk HPV negative subgroup. On multivariable analyses a marginal expression pattern was associated with absent lymph node metastases (OR 0.4) while diffuse expression was associated with poor survival (HR 2.58).
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| 27692344 | Lung Carcinoma | Inhibit immunity | Chemoresistance is a major challenge in lung cancer treatment. This induction correlated with reduction in expression of drug resistance genes MDR1, MRP1, ABCG2 and ABCC2 along with decreased expression of PD-L1 which is associated with severe dysfunction of tumor specific CD8+ T cells.
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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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| 27623354 | Clear Cell Renal Cell Carcinoma | Inhibit immunity (T cell function); immunotherapy target | Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor that is characterized in most cases by inactivation of the tumor suppressor gene VHL. PD-L1 expression was observed in 69 ccRCC (70.4%) and the corresponding patients had a worse prognosis, with a median specific survival of 52 months (p?=?0.03). PD-L1 expression was significantly associated with poor prognostic factors such as a higher ISUP nucleolar grade (p?=?0.01), metastases at diagnosis (p?=?0.01), a sarcomatoid component (p?=?0.04), overexpression of VEGF (p?=?0.006), and cytoplasmic PAR-3 expression (p?=?0.01). Interestingly, all wild-type VHL tumors (no VHL gene alteration, 11.2%) expressed PD-L1. In this study, we found PD-L1 expression to be associated with noninactivated VHL tumors and in particular wild-type VHL ccRCC, which may benefit from therapies inhibiting PD-L1/PD-1.
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| 29351920 | Ovarian Carcinoma | Inhibit immunity | Heavy infiltration of the PD-L1-mutated and PD-L1-overexpressing tumor with T cell lymphocytes (ie, CD4+/CD8+ TIL), CD68+ macrophages and CD20+ B cells was detected in the surgical specimen strongly suggesting immune evasion as a key mechanism of tumor growth and survival.
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| 29337305 | Ovarian carcinoma; Melanoma | Inhibit immunity (T/NK cell function); immunotherapy target | Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade-mediated tumor regression. Here, we evaluated 3 tumor-bearing mouse models that differ in their sensitivity to PD-L1 blockade and demonstrated a loss of therapeutic efficacy of PD-L1 blockade in immunodeficient mice and in PD-L1- and PD-1-deficient mice. Additionally, expression of PD-L1 on dendritic cells and macrophages in ovarian cancer and melanoma patients correlated with the efficacy of treatment with either anti-PD-1 alone or in combination with anti-CTLA-4.
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| 29320474 | Desmoplastic Melanoma | Inhibit immunity | High response rate to PD-1 blockade in desmoplastic melanomas. Immunohistochemistry analysis from nineteen desmoplastic melanomas and thirteen non-desmoplastic melanomas revealed a higher percentage of PD-L1-positive cells in the tumour parenchyma in desmoplastic melanomas (P?=?0.04); these cells were highly associated with increased CD8 density and PD-L1 expression in the tumour invasive margin.
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| 24548766 | Lung Adenocarcinoma | Inhibit immunity | There may be a possibility for immunotherapy targeting the PD-L1 pathway in patients with lung adenocarcinoma in the future.
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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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| 25964311 | Glioblastoma | Inhibit immunity | Earlier evidence suggested that PD-L1 expression may contribute to immunoresistance of human glioblastoma cells via activation of the PI3K/mTOR pathway and that loss of PTEN function appeared to change the level of PD-L1 expression. PD-L1 is a potential immunotherapy target.
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| 16482562 | Renal Cell Carcinoma; Melanoma | Inhibit immunity (T cell function); immunotherapy target | Blockade of PD-L1 (B7-H1) augments human tumor-specific T cell responses in vitro. We found PD-L1 to be constitutively expressed on human renal cell carcinoma (RCC) cell lines and upregulated on human melanoma cell lines upon exposure to interferon-gamma.Similar to the data achieved in the murine system, the blockade of PD-L1 on human tumors resulted in enhanced cytolytic activity of TAA-specific CTLs and cytokine production of TAA-specific T helper cells when interacting directly with the tumor.
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| 27418644 | Plasma cell myeloma | Inhibit immunity | The immune checkpoint molecules programmed death ligand 1 (PD-L1), Galectin-9, herpesvirus entry mediator (HVEM), and CD200, as well as T-cell metabolism regulators indoleamine 2, 3-dioxygenase (IDO), and CD38 are significantly upregulated during osteoclastogenesis. Importantly, the levels of these molecules, except CD38, are higher in OCs than in MM cells. Anti-PD-L1 monoclonal antibody (mAb) and IDO inhibitor partly overcome OC-inhibited T-cell responses against MM cells, confirming their roles in OC-suppressed MM cell lysis by cytotoxic T cells.
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| 27404452 | Colorectal carcinoma | Inhibit immunity | However, PD-L1+(I) MSI-H CRCs were characterised by high-density tumour-infiltrating immune cells, including T cells and macrophages, and intense peritumoural lymphoid reactions.
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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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| 23095323 | Melanoma | Inhibit immunity (T cell function) | MEKi in melanoma cells shows dual therapeutic effects with simultaneous suppression of PD-L1 expression and induction of apoptosis. By combining MEKi with BRAFi, an additive effect on the inhibition of PD-L1 expression results.
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| 19451266 | Hepatocellular carcinoma | Inhibit immunity (T cell function) | Monocytes activated by tumors strongly express PD-L1 proteins with kinetics similar to their activation status, and significant correlations were found between the levels of PD-L1(+) and HLA-DR(high) on tumor-infiltrating monocytes. Autocrine tumor necrosis factor alpha and interleukin 10 released from activated monocytes stimulated monocyte expression of PD-L1. The PD-L1(+) monocytes effectively suppressed tumor-specific T cell immunity and contributed to the growth of human tumors in vivo; the effect could be reversed by blocking PD-L1 on those monocytes.
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| 19264916 | Glioblastoma | Inhibit immunity; immunotherapy target | Human glioblastoma is well known for its capacity to interfere with effective antitumor immune responses. B7-H1 is the third member of the B7 family that plays important roles in tumor immune evasion. B7-H1 was significantly upregulated at the growing edge of the tumors.
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| 28483787 | Breast Neoplasm | Inhibit immunity (T cell function); essential for immunotherapy | Immune cell infiltrates of untreated tumor-bearing neu/N mice expressed high numbers of PD1 and OX40 receptors on their CD8+T cells, and PD-L1 was highly expressed on both myeloid and tumor cells. Modulating PD-L1 and OX40 receptor signaling combined with intratumoral ADU S-100 administration enhanced HER-2-specific CD8+T-cell activity, clearing tumors in 40% of neu/N mice.
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| 28470686 | Pancreatic Carcinoma; Ampulla of Vater Carcinoma | Inhibit immunity (T cell function) | Our aim was to examine the expression of the immune inhibiting molecules PD-L1, Galectin-9, HVEM, IDO and HLA-G, as well as CD8+ and FoxP3+ tumor infiltrating lymphocytes (TIL), in pancreatic and ampullary cancers, and to relate their individual, as well as their combined expression, to cancer survival. Expression of immune inhibitory molecules and TIL was examined by immunohistochemistry. We show that immune inhibitory molecules are prevalently expressed. Moreover, high tumor expression of PD-L1 (p?=?0.002), Gal-9 (p?=?0.003), HVEM (p?=?0.001), IDO (p?=?0.049), HLA-G (p?=?0.004) and high CD8/FoxP3 TIL ratio (p?=?0.006) were associated with improved cancer-specific survival.
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| 23613317 | Glioma | Inhibit immunity (T cell function) | Stimulation of monocytes with IL-10 alone could significantly increase B7-H1 expression, sufficient to induce T-cell apoptosis when cocultured with stimulated monocytes. Gliomas can upregulate B7-H1 expression in circulating monocytes and tumor-infiltrative macrophages through modulation of autocrine/paracrine IL-10 signaling, resulting in an immunosuppressive phenotype.
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| 23580578 | Lung Carcinoma | Inhibit immunity (T cell function) | Immunomodulatory antibodies directed against cytotoxic T cell-associated antigen 4 (CTLA-4/CD152) and programmed cell death ligand 1 (PDL1/CD274) showed clinical efficacy in patients with lung cancer.
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| 23455497 | Breast Carcinoma | Inhibit immunity (T cell function) | Importantly, tumor-associated neutrophils strongly bound B7x protein and inhibited the proliferation of both CD4 and CD8 T cells. These results suggest that host B7x may enable metastasizing cancer cells to escape local antitumor immune responses through interactions with the innate and adaptive immune systems.
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| 29090321 | Hepatocellular Carcinoma | Inhibit immunity (T cell function) | In the present study, we asked whether TNF-α can promote the expression of B7-H1 induced by IFN-γ in HCC cells. We found that JAK/STAT1/IRF1 was the primary pathway responsible for induction of B7-H1 expression by IFN-γ in human HCC cell lines. TNF-α and IFN-γ synergistically induced the expression of B7-H1 in the HCC cells. Moreover, the mechanism of the synergy was that TNF-α enhanced IFN-γ signaling by upregulating the expression of IFN-γ receptors.
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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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| 18203952 | Hodgkin lymphoma | Inhibit immunity (T cell function) | Blockade of the PD-1 signaling pathway inhibited SHP-2 phosphorylation and restored the IFN-gamma-producing function of HL-infiltrating T cells. According to these results, deficient cellular immunity observed in HL patients can be explained by "T-cell exhaustion," which is led by the activation of PD-1-PD-L signaling pathway.
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| 17415709 | Breast Carcinoma | Inhibit immunity | B7-H1, a co-inhibitory molecule, plays a role in immune escape of tumors. We have shown for the first time a direct association between proliferation and the expression of B7-H1 in breast cancer patients.
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| 17363736 | Multiple Myeloma-IgG | Inhibit immunity (T cell function); immunotherapy target | We observed that B7-H1 was expressed in most MM plasma cells, but not cells isolated from monoclonal gammopathy of undetermined significance or healthy donors. This expression was increased or induced by IFN-gamma and Toll-like receptor (TLR) ligands in isolated MM plasma cells. Blocking the MEK/ERK pathway inhibited IFN-gamma-mediated and TLR-mediated expression of B7-H1. Inhibition of the MyD88 and TRAF6 adaptor proteins of the TLR pathway blocked not only B7-H1 expression induced by TLR ligands but also that mediated by IFN-gamma. IFN-gamma-induced STAT1 activation, via MEK/ERK and MyD88/TRAF6, and inhibition of STAT1 reduced B7-H1 expression. MM plasma cells stimulated with IFN-gamma or TLR ligands inhibited cytotoxic T lymphocytes (CTLs) generation and this immunosuppressive effect was inhibited by preincubation with an anti-B7-H1 antibody, the UO126 MEK inhibitor, or by transfection of a dominant-negative mutant of MyD88.
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| 27470968 | Gastrointestinal Stromal Tumor | Inhibit immunity (T cell function); immunotherapy target | PD-1/PD-L1 Blockade Enhances T-cell Activity and Antitumor Efficacy of Imatinib in Gastrointestinal Stromal Tumors.
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| 27463676 | Melanoma | Inhibit immunity (T cell function) | Interferon-γ (IFN-γ)-induced PD-L1 up-regulation on MB requires Cdk5, and disruption of Cdk5 expression in a mouse model of MB results in potent CD4(+) T cell-mediated tumor rejection.
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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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| 28407528 | Non-small Cell Lung Carcinoma | Inhibit immunity (T cell function); immnotherapy target | Results from recent phase II and phase III randomised trials testing other ICIs have been presented. In Keynote-024, pembrolizumab, an anti-PD1 antibody, was reported to have great efficacy in the first-line treatment of PDL1?≥?50% tumours (30% of screened tumours), with a progression-free survival (PFS, median) of 10.4 months versus 6.0 months with chemotherapy (CT; hazard ratio [HR]?=?0.50; 95% confidence interval [95% CI] 0.37-0.68, P? |
| 28368722 | Melanoma; Ovarian Carcinoma | Inhibit immunity (T cell function) | Our recent report shows that tumor cell-intrinsic CD274 promotes MTORC1 signaling in mouse melanoma and mouse and human ovarian cancer, inhibits autophagy and sensitizes some tumors to clinically available pharmacological autophagy inhibitors and confers resistance to MTOR inhibitors. Tumor CD274 could be a biomarker of autophagy or MTOR inhibitor response in selected tumors, and these inhibitors could improve anti-CD274 or anti-PDCD1 cancer immunotherapy.
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| 28302645 | Melanoma; Colorectal Adenocarcinoma | Inhibit immunity (T cell function) | We used three mouse tumor models sensitive to PD-1 blockade to evaluate the significance of PD-L1 on tumor versus nontumor cells. PD-L1 on nontumor cells is critical for inhibiting antitumor immunity in B16 melanoma and a genetically engineered melanoma. In contrast, PD-L1 on MC38 colorectal adenocarcinoma cells is sufficient to suppress antitumor immunity, as deletion of PD-L1 on highly immunogenic MC38 tumor cells allows effective antitumor immunity. MC38-derived PD-L1 potently inhibited CD8+ T cell cytotoxicity. Wild-type MC38 cells outcompeted PD-L1-deleted MC38 cells in vivo, demonstrating tumor PD-L1 confers a selective advantage. Thus, both tumor- and host-derived PD-L1 can play critical roles in immunosuppression. Our findings establish reduced cytotoxicity as a key mechanism by which tumor PD-L1 suppresses antitumor immunity and demonstrate that tumor PD-L1 is not just a marker of suppressed antitumor immunity.
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| 24848257 | Rhabdomyosarcoma | Inhibit immunity (T cell function) | Murine RMS showed high surface expression of PD-L1, and anti-PD1 prevented tumor growth if initiated early after tumor inoculation; however, delayed anti-PD1 had limited benefit.
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| 24778419 | Melanoma; Lung Carcinoma; Colon Carcinoma; Breast Carcinoma | Inhibit immunity (T cell function) | We demonstrate that MDSCs at the tumor site show a differential expression of PD-L1 as compared with MDSCs from peripheral lymphoid organ (spleen). Hypoxia caused a rapid, dramatic, and selective up-regulation of PD-L1 on splenic MDSCs in tumor-bearing mice. This was not limited to MDSCs, as hypoxia also significantly increased the expression of PD-L1 on macrophages, dendritic cells, and tumor cells. Blockade of PD-L1 under hypoxia enhanced MDSC-mediated T cell activation and was accompanied by the down-regulation of MDSCs IL-6 and IL-10.
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| 19826049 | Hepatocellular Carcinoma | Inhibit immunity (T cell function) | PD-1(+)CD8(+) T cells had decreased proliferative ability and effector function as shown by reduced granule and cytokine expression compared with PD-1(-) T cells. Importantly, blocking KC B7-H1 interaction with PD-1(+)CD8(+) cells using neutralizing antibodies recovered effector T-cell function.
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| 19710456 | Melanoma | Inhibit immunity (T cell function) | Depletion or blockade of B7-H1 on activated DCs increased the magnitude of effector CD8 T cell expansion. DC-based or protein-based tumor vaccines, in combination with B7-H1 blockade, induced strong effector CD8 T cell responses, resulting in protective immunity against newly established tumors.
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| 19188168 | Hepatocellular Carcinoma | Inhibit immunity | Patients with higher expression of PD-L1 had a significantly poorer prognosis than patients with lower expression. Although patients with higher expression of PD-L2 also had a poorer survival, the difference in recurrence was not statistically significant. Multivariate analysis identified tumor expression of PD-L1 as an independent predictor for postoperative recurrence.
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| 29435131 | Non-Small Cell Lung Carcinoma | Inhibit immunity (T cell function) | Mechanistic studies indicated that upregulation of YAP1 by PD-L1 might be responsible for EGFR mutation-independent TKI resistance via the ROS/HIF-1α axis. An unfavorable TKI response was more common in patient tumors with high PD-L1 or YAP1 mRNA expression than in patient tumors with low mRNA expression of these genes.
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| 29656492 | melanoma | Inhibit immunity (T cell function) | Cancer cells resist to the host immune antitumor response via multiple suppressive mechanisms, including the overexpression of PD-L1 that exhausts antigen-specific CD8+ T cells through PD-1 receptors.
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| 29603856 | colorectal carcinoma | Inhibit immunity (T cell function) | Immune checkpoint inhibitors (ICIs) block CTLA-4, PD-1 and PD-L1, or other molecules that control antitumour activities of lymphocytes.
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| 29580288 | Plasma Cell Myeloma | Inhibit immunity (T cell function) | Drugs modulating the transcriptional and post-transcriptional regulation of PD-L1 could represent new therapeutic strategies for the treatment of multiple myeloma, help potentiate the action of other drugs or be combined to PD-1/PD-L1 inhibitors in order to avoid the potentially problematic combination with immunomodulators.
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| 27925176 | Breast Carcinoma | Inhibit immunity (T cell function) | The expression of PD-L1 and tumor-infiltrating lymphocytes (TILs) in residual breast cancer cells was assessed by immunohistochemistry in surgical specimens. High expression of PD-L1 was correlated to worse survival. The expression of PD-L1 was more commonly observed in patients with low levels of total TILs (p? |
| 27813511 | Colorectal Cancinoma | Inhibit immunity; immunotherapy target | The CD274 (PD-L1)/PDCD1 (PD-1) pathway is crucial for the modulation of immune responses and self-tolerance. Aberrantly expressed CD274 allows tumor cells to evade host immune system and is considered to be a mechanism of adaptive immune resistance. Inhibition of the CD274/PDCD1 immune checkpoint offers a promising new therapeutic strategy. In this study, 454 primary colorectal carcinomas were analyzed histologically and immunohistochemically for CD274, mismatch repair (MMR) proteins, intestinal differentiation marker (CDX2), and stem cell markers (ALCAM, ALDH1A1, and SALL4). Thus, colorectal carcinomas defined by CD274 positivity displayed features associated with tumors arising via the serrated neoplasia pathway.
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| 27797936 | Pancreatic Ductal Adenocarcinoma | Immunotherapy target | These preclinical results indicate that targeted inhibition of IL-6 may enhance the efficacy of anti-PD-L1 in PDAC.
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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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| 24030703 | Hepatocellular Carcinoma | Inhibit immunity (T cell function) | Anti-B7-H1 (PD-L1) monoclonal antibodies (mAb) block a critical inhibitory pathway in T cells, whereas anti-CD137 and OX40 mAbs provide T-cell costimulation.
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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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| 23986400 | Melanoma | Inhibit immunity (T cell function) | In the current report, we show that it is the subset of T cell-inflamed tumors that showed high expression of three defined immunosuppressive mechanisms: indoleamine-2,3-dioxygenase (IDO), PD-L1/B7-H1, and FoxP3(+) regulatory T cells (T(regs)), suggesting that these inhibitory pathways might serve as negative feedback mechanisms that followed, rather than preceded, CD8(+) T cell infiltration.
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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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| 21540239 | B-Cell Non-Hodgkin Lymphoma | Inhibit immunity (T cell function) | Programmed death ligand 1 is expressed by non-hodgkin lymphomas and inhibits the activity of tumor-associated T cells. In autologous cultures of primary ALCL and DLBCL, PD-L1 blockade enhanced secretion of inflammatory cytokines IFN-γ, granulocyte macrophage colony-stimulating factor, interleukin (IL)-1, IL-6, IL-8, IL-13, TNF-α, and macrophage inflammatory protein-1α. In establishing cell lines from an aggressive PD-L1(+) mature B-cell lymphoma, we also noted that PD-L1 expression could be lost under certain in vitro culture conditions.
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| 21536144 | Plasma Cell Myeloma | Inhibit immunity (T cell function) | Immunosuppressive effects of multiple myeloma are overcome by PD-L1 blockade. These data demonstrate a role for PD-L1 in suppressing immune responses to myeloma and suggest that blockade of this pathway may enhance immunotherapy for this disease.
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| 21385853 | Acute Myeloid Leukemia | Inhibit immunity | 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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| 20007574 | Mesothelioma | Inhibit immunity (T cell function) | One of these is expression of T cell inhibitory ligands such as programmed death-ligand 1 (PD-L1; B7-H1). In this study, we show that PD-L1 is highly expressed on mesothelioma tumor cells and within the tumor stroma. Thus, PD-L1 blockade activates antitumor CD8 T cell most potently in the absence of CD4 T cells.
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| 29361059 | Renal Cell Carcinoma | Inhibit immunity | PD-1, PD-L2, CTLA4 and FOXP3, all of which are implicated in the evasion of an anti-tumor immune response, had a significantly higher expression for samples representing co-detection of productive TcR-α and -β recombination reads.
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| 29345842 | Gastric Carcinoma | Inhibit immunity | In particular, programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) are widely known as important immune checkpoint molecules associated with the mechanisms of immune escape by malignant tumor cells.
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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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| 29307625 | Vulvar Melanoma | Inhibit immunity (T cell function) | PDL1 expression >5% and peritumoral CD8+, peritumoral FoxP3+, and tumoral FoxP3+ lymphocytes correlated with better overall survival. Tumoral PDL1 expression correlated with tumoral as well as peritumoral CD8+ and FoxP3+ lymphocytes, supportive of an adaptive immune response. Although the frequency of PDL1 expression is low in vulvar melanoma, its expression may identify a subset of vulvar melanoma that might respond to immunotherapy.
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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 | 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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| 29233903 | Head and Neck Carcinoma | Inhibit immunity | HNSCCs expressing elevated levels of PD-L1 have especially poor outcome. PD-L1 levels on exosomes, but not levels of sPD-L1, associated with disease progression in HNSCC patients. Circulating PD-L1+exosomes emerge as useful metrics of disease and immune activity in HNSCC patients.
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| 28892778 | Non-Small Cell Lung Carcinoma | Inhibit immunity (T cell function) | An increase in BAG-1 by PD-L1 confers resistance to tyrosine kinase inhibitor in non-small cell lung cancer via persistent activation of ERK signalling. Mechanistically, the PD-L1-induced BAG-1 expression reciprocally increased PD-L1 expression due to persistent activation of ERK signalling, and it consequently conferred TKI resistance in NSCLC cells.
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| 28822887 | Non-Small Cell Lung Carcinoma | Inhibit immunity (T cell function); Immunotherapy target | Recently, immunotherapy based on programmed cell death 1 (PD-1) and its ligand (PD-L1) blockade prolong survival in patients with advanced NSCLC, especially in those patients with positive expression of PD-L1 and when used in the first-line setting.
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| 28819064 | Non-Small Cell Lung Carcinoma | Inhibit immunity (T cell function); Immunotherapy target | Immune checkpoint inhibitors targeting the interaction between programmed cell death-1 (PD-1) and its ligand PD-L1 induce tumor regression in a subset of non-small cell lung cancer patients. Silencing PD-L1 expression in CMT167 cells resulted in smaller orthotopic tumors that remained sensitive to anti-PD-L1 therapy, whereas implantation of CMT167 cells into PD-L1-mice blocked orthotopic tumor growth, indicating a role for PD-L1 in both the cancer cell and the microenvironment.
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| 28809532 | Pancreatic Carcinoma | Inhibit immunity (T cell function) | We also found that CXCL12 trap allowed T-cell penetration into the tumor, and PD-L1 trap allowed the infiltrated T-cells to kill the tumor cells.
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| 28648905 | Hepatocellular Carcinoma | Inhibit immunity (T cell function) | Expression of PD-1, TIM3, LAG3, and CTLA4 was significantly higher on CD8+and CD4+T cells isolated from HCC tissue than control tissue or blood. Compared with TIL that did not express these inhibitory receptors, CD8+and CD4+TIL that did express these receptors had higher levels of markers of activation, but similar or decreased levels of granzyme B and effector cytokines.
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| 28073774 | Sarcoma | Inhibit immunity | Using CRISPR/Cas9-induced loss-of-function approaches and overexpression gain-of-function techniques, we confirmed that PD-L1 on tumor cells is key to promoting tumor escape.In addition, the capacity of PD-L1 to suppress antitumor responses was inversely proportional to tumor cell antigenicity. PD-L1 expression on host cells, particularly tumor-associated macrophages (TAM), was also important for tumor immune escape.
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| 24336068 | Prostate Carcinoma | Inhibit immunity | Hypoxia-induced expression of PD-L1 in cancer cells increased their resistance to CTL-mediated lysis. We found that higher expression of PD-L1 induced in tumor cells by exposure to hypoxia led to increased apoptosis of cocultured CTLs and Jurkat leukemia T cells.
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| 24302925 | Ovarian Carcinoma | Inhibit immunity | Expression of both B7-H1 and IDO are associated with differentiation and recruitment of Treg, and clinical studies have shown that each of these mechanisms correlates independently with increased morbidity and mortality in ovarian cancer patients.
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| 24089443 | Melanoma | Inhibit immunity; Immunotherapy target | Immune checkpoint blockade with monoclonal antibodies directed at the inhibitory immune receptors CTLA-4, PD-1, and PD-L1 has emerged as a successful treatment approach for patients with advanced melanoma.
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| 21659460 | Leukemia | Inhibit immunity | PD-L1 was highly upregulated on immature human leukemic progenitor cells, whereas costimulatory molecules such as CD80 and CD86 were not expressed. Blocking PD-1 signaling using human antibodies led to elevated proliferation and IFN-γ production of MiHA-specific T cells cocultured with PD-L1-expressing leukemia cells. Taken together, our findings indicate that the PD-1/PD-L pathway can be hijacked as an immune escape mechanism in hematological malignancies.
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| 20626886 | Breast Carcinoma | Inhibit immunity | Interestingly, siRNA knock down of B7-H1 lead to an increase in spontaneous apoptosis, as well as doxorubicin-induced apoptosis, which indicates an anti-apoptotic role for B7-H1 in breast cancer cells.
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| 20570856 | Acute Myeloid Leukemia | Inhibit immunity (T cell function) | Program death-1 signaling and regulatory T cells collaborate to resist the function of adoptively transferred cytotoxic T lymphocytes in advanced acute myeloid leukemia. These data demonstrated that interaction between PD-1 and PD-L1 can facilitate Treg-induced suppression of T-effector cells and dampen the antitumor immune response.
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| 20194714 | Melanoma | Inhibit immunity (T cell function) | In this study, in vitro blockade of PD-L1 interaction on DCs led to enhanced IFN-gamma production and cytotoxicity by Ag-specific T cells. Together, these studies support the blocking of PD-L1 signaling as a means to enhance combined immunotherapy approaches against melanoma.
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| 29855617 | Cervical Carcinoma | Inhibit immunity | We report that PD-L1 is overexpressed in CC, and shRNA-mediated PD-L1 depletion suppresses the proliferation, invasion, and tumorigenesis of CC cells.
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| 29757193 | Triple-Negative Breast Carcinoma | Inhibit immunity | Eya3 promotes breast tumor-associated immune suppression via threonine phosphatase-mediated PD-L1 upregulation. We show that Myc is required for Eya3-mediated increases in PD-L1, and that rescue of PD-L1 in Eya3-knockdown cells restores tumor progression.
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| 29721396 | Breast Carcinoma; Colon Carcinoma | Inhibit immunity; Immunotherapy target | Secretion of TGFβ and upregulation of immune checkpoint programmed cell death ligand-1 (PD-L1) are two main contributors to immune evasion and tumor progression. Here, we examined the efficacy of a first-in-class bifunctional checkpoint inhibitor, the fusion protein M7824, comprising the extracellular domain of human TGFβRII (TGFβ Trap) linked to the C-terminus of human anti-PD-L1 heavy chain (αPD-L1). We demonstrate that M7824 reduces plasma TGFβ1, binds to PD-L1 in the tumor, and decreases TGFβ-induced signaling in the tumor microenvironment in mice. These findings demonstrate the value of using M7824 to simultaneously target TGFβ and PD-L1/PD-1 immunosuppressive pathways to promote anti-tumor responses and efficacy.
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| 29721192 | Medulloblastoma | Inhibit immunity | MB expresses low levels of PD-L1 facilitating immune escape.
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| 18850006 | Breast Carcinoma; Prostate Carcinoma | Inhibit immunity | B7-H1-mediated immunoresistance can be attenuated by inhibitors of the PI(3) kinase pathway, and is dependent on S6K1-mediated translational regulation of B7-H1 protein. Breast and prostate carcinoma cells with activated PI(3) kinase lose the immunoresistant phenotype after treatment with B7-H1 siRNA. Conversely, breast and prostate carcinoma cells with minimal PI(3) kinase activation adopt an immunoresistant phenotype when engineered to overexpress B7-H1 protein.
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| 16208700 | Metastatic Renal Cell Cancer | Inhibit immunity | Patients with high expression of B7-H1 on primary tumor cells and/or lymphocytes were significantly more likely to die of RCC compared with patients with low B7-H1 expression (risk ratio [RR] = 4.17; 95% confidence interval [95% CI], 1.97-8.84; P < 0.001) and this risk persisted in multivariate analysis after adjusting for the Mayo Clinic stage, size, grade, and necrosis score (RR = 2.63; 96% CI, 1.23-5.64; P = 0.013).
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| 25193987 | renal cell carcinoma | Inhibit immunity | In non-ccRCC, patients with PD-L1+ tumors appear to have worse clinical outcomes, although only PD-L1 positivity in tumor cells is associated with higher tumor stage and grade
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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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