RIG-I is an intracellular checkpoint that limits CD8+ T-cell antitumour immunity

被引：2

作者：

Duan, Xiaobing ^{[1
,2
]}

Hu, Jiali ^{[1
]}

Zhang, Yuncong ^{[1
]}

Zhao, Xiaoguang ^{[1
]}

Yang, Mingqi ^{[1
]}

Sun, Taoping ^{[3
]}

Liu, Siya ^{[4
]}

Chen, Xin ^{[2
]}

Feng, Juan ^{[2
]}

Li, Wenting ^{[1
]}

Yang, Ze ^{[1
]}

Zhang, Yitian ^{[1
]}

Lin, Xiaowen ^{[1
]}

Liu, Dingjie ^{[1
]}

Meng, Ya ^{[1
]}

Yang, Guang ^{[1
]}

Lin, Qiuping ^{[3
]}

Zhang, Guihai ^{[5
]}

Lei, Haihong ^{[6
]}

Yi, Zhengsheng ^{[6
]}

Liu, Yanyan ^{[1
]}

Liang, Xiaobing ^{[7
]}

Wu, Yujuan ^{[8
]}

Diao, Wenqing ^{[8
]}

Li, Zesong ^{[9
]}

Liang, Haihai ^{[1
,10
]}

Zhan, Meixiao ^{[1
,11
]}

Sun, Hong-Wei ^{[1
]}

Li, Xian-Yang ^{[1
]}

Lu, Ligong ^{[1
,11
]}

机构：

[1] Jinan Univ, Zhuhai Peoples Hosp, Zhuhai Clin Med Coll, Guangdong Prov Key Lab Tumour Intervent Diag & Tre, Zhuhai 519000, Peoples R China

[2] Foshan Univ, Gene Editing Technol Ctr Guangdong Prov, Sch Med, Foshan 528225, Peoples R China

[3] Jinan Univ, Zhuhai Peoples Hosp, Zhuhai Clin Med Coll, Zhuhai Precis Med Ctr, Zhuhai 519000, Peoples R China

[4] Third Peoples Hosp Zhuhai, Zhuhai 519000, Peoples R China

[5] Jinan Univ, Zhuhai Peoples Hosp, Zhuhai Clin Med Coll, Dept Oncol, Zhuhai 519000, Peoples R China

[6] Jinan Univ, Zhuhai Peoples Hosp, Zhuhai Clin Med Coll, Dept Radiat Oncol, Zhuhai 519000, Peoples R China

[7] Guangdong Huixin Life Sci Co, Zhuhai 519000, Peoples R China

[8] Zhuhai Cent Blood Stn, Zhuhai 519000, Peoples R China

[9] Shenzhen Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp 2, Shenzhen Inst Translat Med,Shenzhen Key Lab Genito, Shenzhen, Peoples R China

[10] Harbin Med Univ, Coll Pharm, Dept Pharmacol, Minist Educ,Key Lab Cardiovasc Res,State Prov Key, Harbin 150081, Peoples R China

[11] South China Univ Technol, Guangzhou Pepoples Hosp 1, Affiliated Hosp 2, Sch Med, Guangzhou 510006, Peoples R China

来源：

EMBO MOLECULAR MEDICINE | 2024年 / 16卷 / 11期

基金：

中国国家自然科学基金;

关键词：

RIG-I; CD8(+) T cells; Immune Checkpoint; AKT/Glycolysis Signalling Pathway; Immunotherapy; ACTIVATION; CARCINOMA;

D O I：

10.1038/s44321-024-00136-9

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Retinoic acid-inducible gene I (RIG-I) is a pattern recognition receptor involved in innate immunity, but its role in adaptive immunity, specifically in the context of CD8(+) T-cell antitumour immunity, remains unclear. Here, we demonstrate that RIG-I is upregulated in tumour-infiltrating CD8(+) T cells, where it functions as an intracellular checkpoint to negatively regulate CD8(+) T-cell function and limit antitumour immunity. Mechanistically, the upregulation of RIG-I in CD8+ T cells is induced by activated T cells, and directly inhibits the AKT/glycolysis signalling pathway. In addition, knocking out RIG-I enhances the efficacy of adoptively transferred T cells against solid tumours, and inhibiting RIG-I enhances the response to PD-1 blockade. Overall, our study identifies RIG-I as an intracellular checkpoint and a potential target for alleviating inhibitory constraints on T cells in cancer immunotherapy, either alone or in combination with an immune checkpoint inhibitor.

引用

页码：3005 / 3025

页数：21

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