Bladder cancer cells induce immunosuppression of T cells by supporting PD‐L1 expression in tumour macrophages partially through interleukin 10

Wang, Xingyuan; Ni, Shaobin; Chen, Qi-Yin; Ma, Li; Jiao, Zhi-Xing; Wang, Chunyang; Chen, Zhangjian

doi:10.1002/cbin.10716

Cited by 46 publications

(33 citation statements)

References 32 publications

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“…The primary bladder tumor cells secrete a large amount of IL-10. Removing IL-10 in co-cultures of monocytes and tumor cells can reduce the upregulation of PD-L1 in monocytes and affect the curative effect of the immune checkpoint inhibitors (Wang et al, 2017). RUNX1 is a novel direct target of miR-27a, which is involved in the regulation of sensitivity to bladder cancer chemotherapy (Deng et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis Finds Immune Gene Markers Related to the Prognosis of Bladder Cancer

et al. 2020

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Bladder cancer is one of the most common malignant tumors of the urinary system that seriously threatens the health of a population. In recent years, the application of immunotherapy has significantly changed the treatment of bladder cancer, but only some patients can benefit from the treatment with immune-checkpoint inhibitors. Many problems are unsolved in the field of bladder cancer immunotherapy, especially in the search for genes that are critical to the level of immune cell infiltration and new effective therapeutic targets. We attempted to use bioinformatics analysis to identify immune gene markers related to the prognosis of bladder cancer and to establish a prognostic signature for bladder cancer patients based on their immune gene expression profiles. We used univariate Cox proportional hazards regression analysis, the least absolute shrinkage and selection operator (LASSO) Cox regression, and multivariate Cox proportional hazards regression analysis from The Cancer Genome Atlas bladder cancer cohort (TCGA-BLCA). Fifteen genes related to prognosis were screened using the survival analysis, correlation analysis, cancer and adjacent cancer differential expression analysis, and mutation analysis. The potential biological role of these genes was determined using survival analysis and principal component analysis (PCA). The receiver operating characteristic (ROC) curve assesses the prognostic value of the predictive signature. The gene ontology (GO), Kyoto Encyclopedia of Gene and Genome (KEGG), Gene set enrichment analysis (GSEA), and other methods were used to reveal the differential gene enrichment in the signaling pathways and cellular processes of high-and low-risk groups. The single-sample GSEA (ssGSEA) method was used to quantify the infiltration levels of 24 immune cells in the tumor immune microenvironment and these immune genes were found to be closely related to the tumor immune microenvironment. In summary, we screened 15 immune genes that were closely related to bladder cancer overall survival (OS) and may be potential prognostic indicators of bladder cancer. They may have research and clinical application value in bladder cancer immunotherapy. We used 15 immune genes to construct a new immune-related gene signature that was verified and could be helpful in improving individualized prognosis of patients with bladder cancer.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis Finds Immune Gene Markers Related to the Prognosis of Bladder Cancer

et al. 2020

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“…It has been reported that inflammation-associated signals by TNF-alpha induce inflammatory monocytes/macrophages expressing PD-L1 in the tumor microenvironment (Hartley et al 2017). Moreover, an inhibitory function of PD-L1 expressing intratumoral macrophages on T-cell proliferation has been observed in tumor tissues (Wang et al 2017). Thus, our results, in the light of these former findings, further support the hypothesis that PD-L1 expressed in intratumoral macrophages might be a tumor-induced protective mechanism against antitumor inflammation in pulmonary NEC.…”

Section: Discussionmentioning

confidence: 99%

Inflammation and PD-L1 expression in pulmonary neuroendocrine tumors

Kasajima¹,

Ishikawa²,

Iwata³

et al. 2018

Endocrine-Related Cancer

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In the light of novel cancer immune therapies, the status of antitumor inflammatory response and its regulation has gained much attention in patients with lung cancer. Ample datasets exist for non-small-cell lung cancer, but those for pulmonary neuroendocrine tumors are scarce and controversial. Here, tumor-associated inflammation, CD8+ cell infiltration and PD-L1 status were evaluated in a cohort of 57 resected carcinoids and 185 resected neuroendocrine carcinomas of the lung (58 large cell carcinomas and 127 small cell carcinomas). Data were correlated with clinicopathological factors and survival. Moderate or high tumor-associated inflammation was detected in 4 carcinoids (7%) and in 37 neuroendocrine carcinomas (20%). PD-L1 immunoreactivity was seen in immune cells of 73 (39%) neuroendocrine carcinomas, while tumor cells were labeled in 21 (11%) cases. Inflammatory cells and tumor cells in carcinoids lacked any PD-L1 expression. In neuroendocrine carcinomas, PD-L1 positivity in immune cells, but not in tumor cells, was associated with intratumoral CD8+ cell infiltration ( < 0.001), as well as with the severity of tumor-associated inflammation ( < 0.001). In neuroendocrine carcinomas, tumor-associated inflammation and PD-L1 positivity in immune cells correlated with prolonged survival and the latter factor was also an independent prognosticator ( < 0.01, hazard ratio 0.4 for overall survival, < 0.001 hazard ratio 0.4 for disease-free survival). Taken together, in neuroendocrine tumors, antitumor inflammatory response and PD-L1 expression are largely restricted to neuroendocrine carcinomas, and in this tumor entity, PD-L1 expression in inflammatory cells is positively correlated to patient survival.

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“…Tumor-related mPD-1 and mPD-L1 contribute to tumor immune escape [ 64 , 65 ]. Immunotherapeutic strategies against malignant tumors using their antagonists have aroused researchers’ intense interest.…”

Section: Introductionmentioning

confidence: 99%

Soluble PD-1 and PD-L1: predictive and prognostic significance in cancer

2017

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The membrane-bound molecules programmed death 1 (PD-1) and its ligand PD-L1 (PD-1/PD-L1) belong to the immune checkpoint pathway. PD-1 pathway downregulates effector T cells in immune response, thereby causing immune suppression. Recent studies have revealed that membrane-bound PD-1 and PD-L1 also have soluble forms. These soluble forms increase the complexity and diversity of the composition and function of the PD-1/PD-L1 signaling pathway. However, the exact roles of these molecules remain unknown. The objective of this systematic review was to elucidate the biological significance of soluble PD-1/PD-L1 in human cancers and evaluate whether they are potential diagnostic, therapeutic, or prognostic biomarkers. We expect to provide new clues for future research on soluble PD-1/PD-L1 pathway in human malignant tumors.

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Bladder cancer cells induce immunosuppression of T cells by supporting PD‐L1 expression in tumour macrophages partially through interleukin 10

Cited by 46 publications

References 32 publications

Bioinformatics Analysis Finds Immune Gene Markers Related to the Prognosis of Bladder Cancer

Bioinformatics Analysis Finds Immune Gene Markers Related to the Prognosis of Bladder Cancer

Inflammation and PD-L1 expression in pulmonary neuroendocrine tumors

Soluble PD-1 and PD-L1: predictive and prognostic significance in cancer

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