TP53TG1/STAT axis is involved in the development of colon cancer through affecting PD-L1 expression and immune escape mechanism of tumor cells

TP53TG1/STAT轴通过影响PD-L1表达及肿瘤细胞免疫逃逸机制参与结肠癌的发生发展

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作者:Wenmin Ji, Wenyan Wang, Yanfang Wei

Abstract

This research is dedicated to investigating the mechanism of programmed cell death ligand 1 (PD-L1) and tumor protein 53 target gene 1 (TP53TG1) in immune regulation of colon cancer (CC). Expressions of TP53TG1, PD-L1 and signal transducers and activators of transcription (STATs) in CC and their correlation were detected through bioinformatics analysis. Effects of PD-L1 and TP53TG1 on the CC were assessed by in vivo and in vitro experiments. Herein, PD-L1 level was negatively correlated with TP53TG1 expression, but was positively correlated with the levels of STATs. Both overexpressed TP53TG1 and PD-L1 antibody reversed the effects of CT26 cells on inhibiting cell proliferation, cytokine secretion and PD-L1 level, and enhancing the cytotoxicity of NK cells and CD8+ T cells. TP53TG1 reduced PD-L1 level by inactivating STATs pathway. Downregulation of PD-L1 increased cytokine secretion and T lymphocyte killing ability, promoted tumor cell apoptosis, and inhibited the tumor growth. Altogether, TP53TG1/STAT axis regulates the immunomodulatory mechanism of CC by reducing PD-L1 expression.

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