Intron retention regulates STAT2 function and predicts immunotherapy response in lung cancer.

ABSTRACT: Immunotherapy benefits only a subset of lung cancer patients, and the molecular determinants of variable outcomes remain unclear. Using long-read RNA-sequencing we mapped the landscape of alternative RNA splicing in human primary lung adenocarcinomas. We identified over 180,000 full-length mRNA isoforms, more than half of which were novel and many of which occurred in immune-related genes, particularly within the type I interferon response pathway. We discovered retained introns in the STAT2 gene that produce altered protein isoforms that regulate immune signaling and interferon responses. Furthermore, STAT2 intron retention levels predicted patient responses to checkpoint inhibitors. These findings position alternative splicing as a key regulator of tumor immune responses an

SUBMITTER: Englander RP 

PROVIDER: S-EPMC12393442 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature