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However, the molecular determinants of variable patient outcomes remain unclear. Using long-read RNA sequencing, we mapped the landscape of alternative RNA splicing in human primary lung adenocarcinomas. We identified more than 149,000 full-length messenger RNA (mRNA) isoforms, more than half of which were unannotated and many that occurred in immune-related genes, particularly within the type I interferon response pathway. We functionally characterized retained introns in the\n                    <jats:italic toggle=\"yes\">STAT2<\/jats:italic>\n                    gene that produced altered protein isoforms that regulated immune signaling and interferon responses and correlated with patient survival after anti\u2013programmed death-ligand 1 (PD-L1) immunotherapy. These findings position alternative splicing as a regulator of tumor immune responses and reveal intron retention in\n                    <jats:italic toggle=\"yes\">STAT2<\/jats:italic>\n                    as an interferon regulatory axis that correlates with PD-L1 checkpoint inhibitor response.\n                  <\/jats:p>","DOI":"10.1126\/science.aea7156","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T18:00:48Z","timestamp":1792692048000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Intron retention regulates STAT2 function and associates with immunotherapy response in lung cancer"],"prefix":"10.1126","volume":"394","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3549-1455","authenticated-orcid":true,"given":"Ryan P.","family":"Englander","sequence":"first","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA."},{"name":"Graduate 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