EMBO Molecular Medicine (Sep 2024)
RIG-I is an intracellular checkpoint that limits CD8+ T-cell antitumour immunity
- Xiaobing Duan,
- Jiali Hu,
- Yuncong Zhang,
- Xiaoguang Zhao,
- Mingqi Yang,
- Taoping Sun,
- Siya Liu,
- Xin Chen,
- Juan Feng,
- Wenting Li,
- Ze Yang,
- Yitian Zhang,
- Xiaowen Lin,
- Dingjie Liu,
- Ya Meng,
- Guang Yang,
- Qiuping Lin,
- Guihai Zhang,
- Haihong Lei,
- Zhengsheng Yi,
- Yanyan Liu,
- Xiaobing Liang,
- Yujuan Wu,
- Wenqing Diao,
- Zesong Li,
- Haihai Liang,
- Meixiao Zhan,
- Hong-Wei Sun,
- Xian-Yang Li,
- Ligong Lu
Affiliations
- Xiaobing Duan
- Guangdong Provincial Key Laboratory of Tumour Interventional Diagnosis and Treatment, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Jiali Hu
- Guangdong Provincial Key Laboratory of Tumour Interventional Diagnosis and Treatment, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Yuncong Zhang
- Guangdong Provincial Key Laboratory of Tumour Interventional Diagnosis and Treatment, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Xiaoguang Zhao
- Guangdong Provincial Key Laboratory of Tumour Interventional Diagnosis and Treatment, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Mingqi Yang
- Guangdong Provincial Key Laboratory of Tumour Interventional Diagnosis and Treatment, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Taoping Sun
- Zhuhai Precision Medical Center, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Siya Liu
- The Third People’s Hospital of Zhuhai
- Xin Chen
- Gene Editing Technology Center of Guangdong Province, School of Medicine, Foshan University
- Juan Feng
- Gene Editing Technology Center of Guangdong Province, School of Medicine, Foshan University
- Wenting Li
- Guangdong Provincial Key Laboratory of Tumour Interventional Diagnosis and Treatment, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Ze Yang
- Guangdong Provincial Key Laboratory of Tumour Interventional Diagnosis and Treatment, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Yitian Zhang
- Guangdong Provincial Key Laboratory of Tumour Interventional Diagnosis and Treatment, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Xiaowen Lin
- Guangdong Provincial Key Laboratory of Tumour Interventional Diagnosis and Treatment, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Dingjie Liu
- Guangdong Provincial Key Laboratory of Tumour Interventional Diagnosis and Treatment, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Ya Meng
- Guangdong Provincial Key Laboratory of Tumour Interventional Diagnosis and Treatment, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Guang Yang
- Guangdong Provincial Key Laboratory of Tumour Interventional Diagnosis and Treatment, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Qiuping Lin
- Zhuhai Precision Medical Center, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Guihai Zhang
- Department of Oncology, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Haihong Lei
- Department of Radiation Oncology, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Zhengsheng Yi
- Department of Radiation Oncology, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Yanyan Liu
- Guangdong Provincial Key Laboratory of Tumour Interventional Diagnosis and Treatment, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Xiaobing Liang
- Guangdong Huixin Life Science Co., Ltd.
- Yujuan Wu
- Zhuhai Central Blood Station
- Wenqing Diao
- Zhuhai Central Blood Station
- Zesong Li
- Guangdong Provincial Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumours, Shenzhen Key Laboratory of Genitourinary Tumour, Department of Urology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital (Shenzhen Institute of Translational Medicine)
- Haihai Liang
- Guangdong Provincial Key Laboratory of Tumour Interventional Diagnosis and Treatment, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Meixiao Zhan
- Guangdong Provincial Key Laboratory of Tumour Interventional Diagnosis and Treatment, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Hong-Wei Sun
- Guangdong Provincial Key Laboratory of Tumour Interventional Diagnosis and Treatment, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Xian-Yang Li
- Guangdong Provincial Key Laboratory of Tumour Interventional Diagnosis and Treatment, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- Ligong Lu
- Guangdong Provincial Key Laboratory of Tumour Interventional Diagnosis and Treatment, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University)
- DOI
- https://doi.org/10.1038/s44321-024-00136-9
- Journal volume & issue
-
Vol. 16,
no. 11
pp. 3005 – 3025
Abstract
Abstract 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.
Keywords
