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

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. Over

SUBMITTER: Duan X 

PROVIDER: S-EPMC11555380 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature