Science study: STAT2 intron retention predicts lung cancer immunotherapy response (HR 0.49)
EricTopol · x · 2026-10-24
Eric Topol highlights a new Science discovery on the previously unknown role of alternative RNA splicing in cancer immunotherapy response. Using long-read RNA sequencing in lung adenocarcinoma, researchers identified 149,673 full-length isoforms (many unannotated) and found that retention of STAT2 intron 12 produces STAT2-ri12, an isoform that inhibits STAT2 activity. In non-small cell lung cancer, patients with high PSI (percent spliced in) of these introns benefited markedly from atezolizumab: HR 0.49 (95% CI 0.31–0.76, p=0.001), while low-PSI patients showed no significant benefit (HR 0.97). Splicing status could serve as a biomarker for immunotherapy response and survival.
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