Dataset Information

Classification of gallbladder cancer by assessment of CD8+ TIL and PD-L1 expression.

ABSTRACT: BACKGROUND:Programmed death ligand 1/2 (PD-L1/PD-L2) expression has been established as a prognostic factor for various solid tumors and as a predictive factor for PD-1 blockade therapy, but scant data on its role in gallbladder cancer (GBC). The aims of this study were to assess the expression of PD-L1/PD-L2 and the density of CD8+ tumor-infiltrating lymphocytes (TIL) from GBC samples and to quantify the association between survival prognosis and these factors. METHODS:CD8+ TILs density and the expression of PD-1, PD-L1, PD-L2 and CD133 were assessed using immunohistochemistry in tumor specimens from 66 patients with gallbladder adenocarcinoma. These indexes were correlated with the clinicopathological features. RESULTS:The rate of PD-L1-positive (PD-L1+) was 54%, which included 18% positivity in tumor cells, and 36% in peritumoral immune stroma. High CD8+ TIL density (CD8high) was observed in PD-L1+ GBC, and PD-L1+ was positively associated with PD-L2+ expression. Regarding prognostic factors, PD-L1+ expression was related to worse overall survival (OS), and CD8high indicated better OS and progression-free survival (PFS). The combination of CD8high with PD-L1+ serves as a prognostic factor for improved OS (P?

SUBMITTER: Lin J

PROVIDER: S-EPMC6064069 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Classification of gallbladder cancer by assessment of CD8<sup>+</sup> TIL and PD-L1 expression.

Lin Jianzhen J Long Junyu J Wan Xueshuai X Chen Jingci J Bai Yi Y Wang Anqiang A Yang Xiaobo X Wu Yan Y Robson Simon C SC Sang Xinting X Zhao Haitao H

BMC cancer 20180728 1

<h4>Background</h4>Programmed death ligand 1/2 (PD-L1/PD-L2) expression has been established as a prognostic factor for various solid tumors and as a predictive factor for PD-1 blockade therapy, but scant data on its role in gallbladder cancer (GBC). The aims of this study were to assess the expression of PD-L1/PD-L2 and the density of CD8<sup>+</sup> tumor-infiltrating lymphocytes (TIL) from GBC samples and to quantify the association between survival prognosis and these factors.<h4>Methods</h4 ...[more]

PMID: 30055582

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Project description:Background: The relationship between the interleukin 17 (IL-17) family of cytokines and breast cancer has been widely studied in recent years. Many studies have revealed increased levels of the cytokine IL-17A in estrogen receptor (ER)-negative or triple-negative breast cancer. Upregulation of IL-17A signaling is associated with increased expression of programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) in breast cancer with low ER expression and may elevate the infiltration of CD8+ T cells in tumor tissue. This study aims to determine whether ER downregulates the expression of PD-1/PD-L1, reduces the infiltration of CD8+ T cells, and affects the immune microenvironment by decreasing T-helper 17 (Th17) cell infiltration and inhibiting IL-17 signaling in breast cancer. Methods: Samples in The Cancer Genome Atlas Breast Cancer dataset were grouped by ER status and the PAM50 intrinsic subtype. The expression of IL-17 family cytokines and Th17 cell signature cytokines were compared between groups. IL-17 signaling pathway-related genes that were differentially expressed according to the ER level were identified. The PD-1 and PD-L1 levels were compared between breast cancer samples with different ER statuses and IL-17A/IL-17F expression levels. Correlation analyses of the expression of PD-1/PD-L1 and IL-17 signaling pathway-related genes were performed. The associations of the expression of IL-17 signaling pathway-related genes with the immune microenvironment were investigated. Results: High levels of ER decreased the expression of IL-17A, IL-17C, and IL-17F but increased the expression of IL-17E (IL25), which acts as a suppressor of IL-17 signaling. The expression levels of Th17 cell signature cytokines were significantly increased in ER-negative breast cancer. The expression levels of genes encoding downstream products of IL-17A/IL-17F signaling were downregulated in breast cancer with high ER expression. Increased expression of PD-1/PD-L1 was associated with ER-negative status, IL-17A-positive status, IL-17F-positive status, and upregulation of IL-17 signaling pathway-related genes in breast cancer. Enhanced IL-17 signal transduction was associated with the elevation of CD8+ T cell infiltration and variation of the immune microenvironment of breast cancer. Conclusion: High estrogen receptor levels decrease PD-1/PD-L1 expression and CD8+ T cell infiltration by suppressing Th17 cell infiltration and IL-17 signal transduction in breast cancer.

Dataset Information

Classification of gallbladder cancer by assessment of CD8+ TIL and PD-L1 expression.

Publications

Classification of gallbladder cancer by assessment of CD8<sup>+</sup> TIL and PD-L1 expression.

Similar Datasets

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