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

作者：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 · 发表于：EMBO Molecular Medicine · 年份：2024 · DOI：10.1038/s44321-024-00136-9 · 被引用次数：13 · 研究领域：Immune cells in cancer、Immune Cell Function and Interaction、Cancer Immunotherapy and Biomarkers

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.