Open AccessDown‐regulation of EOMES drives T‐cell exhaustion via abolishing EOMES‐mediated repression of inhibitory receptors of T cells in liver cancer
Author(s) -
He Hongwei,
Yi Yong,
Cai Xiaoyan,
Wang Jiaxing,
Ni Xiaochun,
Fu Yipeng,
Qiu Shuangjian
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15898
Subject(s) - biology , inhibitory postsynaptic potential , receptor , carcinogenesis , transcription factor , cancer research , psychological repression , cell , microbiology and biotechnology , cancer cell , cancer , endocrinology , genetics , gene expression , gene
T‐cell exhaustion is one of the hallmarks in cancer, but the mechanisms underlying T‐cell dysregulation remains unclear. Here, we reported that down‐regulation of transcription factor EOMES contributed to increased levels of inhibitory receptors in T cell among the tumour tissues and resulted in the poor prognosis of hepatocellular carcinoma (HCC). By analysing the correlation between EOMES in tumour‐infiltrating T cells and the clinical features, we demonstrated that the EOMES was related to the advanced stage and poor prognosis of HCC. Further mechanistic studies revealed that the EOMES mainly expressed in the CD8 + T cells and were down‐regulated in tumour samples. Moreover, we demonstrated that the EOMES directly bound at the transcriptional regulatory regions of the key inhibitory factors including PD‐1, CTAL‐4 and CD39, and lower levels of EOMES contributed to overexpression of these factors in T cells. Together, our studies provide new insight into the transcriptional deregulation of the inhibitory receptors on T cells during the tumorigenesis.