<scp>TREX1</scp> , a predator for treating <scp>MSI</scp> ‐H tumors?

Immunotherapy has revolutionized cancer treatment; yet, a subset of patients with microsatellite instability-high (MSI-H) tumors fails to respond to treatment despite their elevated tumor mutational burden and immunogenic potential. In a recent study, Xu et al. uncover a key mechanism of immune evasion in MSI-H tumors mediated by the exonuclease TREX1, which degrades cytosolic DNA and suppresses activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING)-type I interferon pathway. Loss of TREX1 restores cytosolic DNA sensing, promotes CD8⁺ T and NK cell infiltration, and enhances antitumor immunity. These findings highlight TREX1 as a potential therapeutic target to overcome resistance to immune checkpoint blockade.