RIG-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. 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.
Competing Interests: Disclosure and competing interests statement XBL is an employee of Huixin Life Science. The authors declare no competing interests.
(© 2024. The Author(s).)