Expression of Id3 represses exhaustion of anti-tumor CD8 T cells in liver cancer

被引：12

作者：

Jin, Yun ^{[1
,3
]}

Hu, Pingping ^{[2
,3
]}

Sun, Haihang ^{[4
]}

Yang, Chao ^{[1
,3
]}

Zhai, Jianxin ^{[1
,3
]}

Wang, Yi ^{[1
,3
]}

Chu, Xinyun ^{[1
,3
]}

Sun, Zhiwei ^{[1
,3
]}

Wang, Jia ^{[4
]}

Sun, Jie ^{[5
]}

Wang, Junfeng ^{[1
,2
,3
]}

机构：

[1] First Peoples Hosp Yunnan Prov, Dept Hepatobiliary Surg, Kunming, Yunnan, Peoples R China

[2] First Peoples Hosp Yunnan Prov, Res Ctr Digital Med, Kunming, Yunnan, Peoples R China

[3] Kunming Univ Sci & Technol, Affiliated Hosp, Kunming, Yunnan, Peoples R China

[4] Linbing Biotechnol Ctr, Jinan, Shandong, Peoples R China

[5] Shanghai Pudong New Area Peoples Hosp, Dept Emergency & Crit Care Med, Shanghai, Peoples R China

来源：

MOLECULAR IMMUNOLOGY | 2022年 / 144卷

基金：

中国国家自然科学基金;

关键词：

Id3; CD8; exhaustion; PD-1; blockade; Liver cancer; LIMITS; PD-1; E2A;

D O I：

10.1016/j.molimm.2022.02.005

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Id3, an inhibitor of DNA binding protein, plays important roles in the function and homeostasis of effector and memory T cells. Recent evidence has shown that Id3 is also implicated in CD8 T cell exhaustion. However, whether and how Id3 might regulate effector function or exhaustion of CD8 T cells, especially in the tumor setting, is still unknown. Here, we first showed that Id3 expression was impaired in tumor-infiltrating CD8 T cells as liver cancer progressed, especially in PD-1+Tim-3 + exhausted CD8 T cells. Enforced expression of Id3 in CD8 T cells resulted in repressed development of anti-tumor CTLs exhaustion, which offered better tumor control. And partially depletion of Id3 in CD8 T cells promoted the development of exhausted CD8 T cells. Furthermore, Id3hi CD8 T cells could respond to PD-1 blockade. Collectively, Id3 exerts protective functions in CD8 T cells for liver cancer.

引用

页码：117 / 126

页数：10

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