RIG-I 是一种限制 CD8 T 细胞抗肿瘤免疫的细胞内检查点。
RIG-I is an intracellular checkpoint that limits CD8+ T-cell antitumour immunity.
发表日期：2024 Sep 25
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
来源：
EMBO Molecular Medicine
摘要：
视黄酸诱导基因 I (RIG-I) 是一种参与先天免疫的模式识别受体，但其在适应性免疫中的作用，特别是在 CD8 T 细胞抗肿瘤免疫中的作用仍不清楚。在这里，我们证明 RIG-I 在肿瘤浸润 CD8 T 细胞中上调，它作为细胞内检查点发挥负向调节 CD8 T 细胞功能并限制抗肿瘤免疫的作用。从机制上讲，CD8 T 细胞中 RIG-I 的上调是由活化的 T 细胞诱导的，并直接抑制 AKT/糖酵解信号通路。此外，敲除 RIG-I 可增强过继转移 T 细胞对抗实体瘤的功效，而抑制 RIG-I 可增强对 PD-1 阻断的反应。总体而言，我们的研究将 RIG-I 确定为细胞内检查点和减轻癌症免疫治疗中 T 细胞抑制限制的潜在靶标，无论是单独使用还是与免疫检查点抑制剂联合使用。© 2024。作者。
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.© 2024. The Author(s).