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

IF 9 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

EMBO Molecular Medicine Pub Date : 2024-09-25 DOI:10.1038/s44321-024-00136-9

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

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引用次数: 0

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.

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RIG-I 是限制 CD8+ T 细胞抗肿瘤免疫的细胞内检查点。

视黄酸诱导基因 I（RIG-I）是一种参与先天性免疫的模式识别受体，但它在适应性免疫，特别是在 CD8+ T 细胞抗肿瘤免疫中的作用仍不清楚。在这里，我们证明了 RIG-I 在肿瘤浸润的 CD8+ T 细胞中上调，它作为细胞内检查点负调控 CD8+ T 细胞功能并限制抗肿瘤免疫。从机理上讲，RIG-I 在 CD8+ T 细胞中的上调是由活化的 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 可增强被收养转移 T 细胞对实体瘤的疗效，抑制 RIG-I 可增强对 PD-1 阻断的反应。总之，我们的研究发现 RIG-I 是一种细胞内检查点，也是在癌症免疫疗法中缓解 T 细胞抑制性限制的潜在靶点，可以单独使用，也可以与免疫检查点抑制剂联合使用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Molecular Medicine 医学-医学：研究与实验

CiteScore

17.70

自引率

0.90%

发文量

105

审稿时长

4-8 weeks

期刊介绍： EMBO Molecular Medicine is an open access journal in the field of experimental medicine, dedicated to science at the interface between clinical research and basic life sciences. In addition to human data, we welcome original studies performed in cells and/or animals provided they demonstrate human disease relevance. To enhance and better specify our commitment to precision medicine, we have expanded the scope of EMM and call for contributions in the following fields: Environmental health and medicine, in particular studies in the field of environmental medicine in its functional and mechanistic aspects (exposome studies, toxicology, biomarkers, modeling, and intervention). Clinical studies and case reports - Human clinical studies providing decisive clues how to control a given disease (epidemiological, pathophysiological, therapeutic, and vaccine studies). Case reports supporting hypothesis-driven research on the disease. Biomedical technologies - Studies that present innovative materials, tools, devices, and technologies with direct translational potential and applicability (imaging technologies, drug delivery systems, tissue engineering, and AI)