biostudies-literatureDuan XShenzhen Municipal Science and Technology Innovation Council | Shenzhen Science and Technology Innovation ProgramGDSTC | Basic and Applied Basic Research Foundation of Guangdong ProvinceGuangdong Provincial Key Laboratory of Construction Foundation ()Guangdong Provincial Key Laboratory of Construction FoundationMOST | National Natural Science Foundation of China (NSFC)the Science and Technology Planning Project of GuangzhouScientific Research start up Project of Zhuhai People's HospitalGDSTC | Basic and Applied Basic Research Foundation of Guangdong Province ()Scientific Research start up Project of Zhuhai People's HospitalShenzhen Municipal Science and Technology Innovation Council | Shenzhen Science and Technology Innovation Program ()MOST | National Natural Science Foundation of China3005-3025https://www.ebi.ac.uk/biostudies/studies/S-EPMC11555380biostudies-literatureUnknown16(11)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. OverEMBO molecular medicineRIG-I is an intracellular checkpoint that limits CD8⁺ T-cell antitumour immunity.PMC115553802020A1515110013823045898210343332200936324709612021A151522018782103306822300672021A1515110561JCYJ202208181018080182024A151501256382044152021B1212040004SL2024A03J005982021KYQD-04Zhang GYi ZLin QLiang XLei HSun HWLin XLiu SMeng YZhao XLiu YZhan MLiang HChen XWu YYang GYang MSun TLi WLu LYang ZLi ZFeng JDiao WHu JZhang YLi XYLiu DDuan XfalseRIG-I is an intracellular checkpoint that limits CD8⁺ T-cell antitumour immunity.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. Over2024-01-01T00:00:00Z2024 Nov2026-07-16T18:41:20.01Z2025-04-06T10:14:28.013ZS-EPMC115553803932286210.1038/s44321-024-00136-9