{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:56:42Z","timestamp":1790661402341,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004080","name":"Korea Drug Development Fund","doi-asserted-by":"publisher","award":["RS\u20102023\u201000283832"],"award-info":[{"award-number":["RS\u20102023\u201000283832"]}],"id":[{"id":"10.13039\/501100004080","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003704","name":"Korea Research Institute of Chemical Technology","doi-asserted-by":"publisher","award":["KK2531\u201020"],"award-info":[{"award-number":["KK2531\u201020"]}],"id":[{"id":"10.13039\/501100003704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003704","name":"Korea Research Institute of Chemical Technology","doi-asserted-by":"publisher","award":["DK2683\u201001"],"award-info":[{"award-number":["DK2683\u201001"]}],"id":[{"id":"10.13039\/501100003704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003704","name":"Korea Research Institute of Chemical Technology","doi-asserted-by":"publisher","award":["KK2632\u201010"],"award-info":[{"award-number":["KK2632\u201010"]}],"id":[{"id":"10.13039\/501100003704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102022R1C1C1006162"],"award-info":[{"award-number":["NRF\u20102022R1C1C1006162"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cancer genomes shape the immune landscape within the tumor microenvironment (TME), thereby influencing host antitumor immunity. Identifying somatic mutations that modulate the TME is critical for selecting patients most likely to benefit from immunotherapy. Here, by integrating a transcriptome\u2010based predictive model with comprehensive genomic analyses, we identified\n                    <jats:italic>SF3B1<\/jats:italic>\n                    splicing factor mutations associated with the response to immune checkpoint inhibitors (ICIs). We systematically evaluated the effects of\n                    <jats:italic>SF3B1<\/jats:italic>\n                    mutations on the TME and ICI response through\n                    <jats:italic>in silico<\/jats:italic>\n                    , in\u00a0vitro, and in\u00a0vivo approaches. Comparative analyses of patient genotypes, together with loss\u2010 and gain\u2010of\u2010function studies, revealed that\n                    <jats:italic>SF3B1<\/jats:italic>\n                    mutations drive transcriptional reprogramming that enhances ICI responsiveness. To validate these findings in\u00a0vivo, we established a syngeneic mouse model using immune\u2010resistant B16F10 melanoma cells. SF3B1\u2010mutant tumors, compared with wild\u2010type counterparts, exhibited TME features and immune profiles indicative of an enhanced antitumor immune response, including increased proportions of CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and dendritic cells, accompanied by the upregulation of immune effectors. Consistently, mice bearing SF3B1\u2010mutant tumors demonstrated significantly greater tumor regression following anti\u2010PD\u20101 treatment compared with their wild\u2010type counterparts. These findings establish\n                    <jats:italic>SF3B1<\/jats:italic>\n                    mutations as predictive biomarkers for guiding rational immunotherapy selection in cancer patients.\n                  <\/jats:p>","DOI":"10.1002\/cam4.72318","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:59:19Z","timestamp":1790657959000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Impact of\n                    <i>SF3B1<\/i>\n                    Mutations on the Tumor Microenvironment and Response to Immunotherapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Kyung\u2010Jin","family":"Cho","sequence":"first","affiliation":[{"name":"Data Convergence Drug Research Center Korea Research Institute of Chemical Technology (KRICT)  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byungho","family":"Lim","sequence":"additional","affiliation":[{"name":"Data Convergence Drug Research Center Korea Research Institute of Chemical Technology (KRICT)  Daejeon Republic of Korea"},{"name":"Department of Medicinal Chemistry and Pharmacology University of Science and Technology (UST)  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"issue":"1","key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41416-018-0327-z","article-title":"The Clinical Role of the TME in Solid Cancer","volume":"120","author":"Giraldo N. A.","year":"2019","journal-title":"British Journal of Cancer"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.79895","article-title":"Cancer Genome and Tumor Microenvironment: Reciprocal Crosstalk Shapes Lung Cancer Plasticity","volume":"11","author":"Mansouri S.","year":"2022","journal-title":"eLife"},{"issue":"3","key":"e_1_2_12_4_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41568-019-0116-x","article-title":"The Evolving Landscape of Biomarkers for Checkpoint Inhibitor Immunotherapy","volume":"19","author":"Havel J. J.","year":"2019","journal-title":"Nature Reviews. Cancer"},{"key":"e_1_2_12_5_1","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2018.00086","article-title":"Anti\u2010PD\u20101 and Anti\u2010CTLA\u20104 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations","volume":"8","author":"Seidel J. A.","year":"2018","journal-title":"Frontiers in Oncology"},{"key":"e_1_2_12_6_1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.coph.2015.05.011","article-title":"PD\u20101\/PD\u2010L1 Inhibitors","volume":"23","author":"Sunshine J.","year":"2015","journal-title":"Current Opinion in Pharmacology"},{"issue":"6","key":"e_1_2_12_7_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/s41568-021-00347-z","article-title":"Systemic Immunity in Cancer","volume":"21","author":"Hiam\u2010Galvez K. J.","year":"2021","journal-title":"Nature Reviews. Cancer"},{"issue":"7559","key":"e_1_2_12_8_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nature14404","article-title":"Melanoma\u2010Intrinsic Beta\u2010Catenin Signalling Prevents Anti\u2010Tumour Immunity","volume":"523","author":"Spranger S.","year":"2015","journal-title":"Nature"},{"issue":"6","key":"e_1_2_12_9_1","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1158\/2159-8290.CD-17-1327","article-title":"Genetic Mechanisms of Immune Evasion in Colorectal Cancer","volume":"8","author":"Grasso C. 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A.","year":"2017","journal-title":"Clinical Cancer Research"},{"key":"e_1_2_12_26_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.7554\/eLife.57243","article-title":"Cancer\u2010Associated Fibroblasts and Their Influence on Tumor Immunity and Immunotherapy","volume":"9","author":"Barrett R. L.","year":"2020","journal-title":"eLife"},{"issue":"1","key":"e_1_2_12_27_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s12916-017-0819-3","article-title":"Successes and Failures: What Did We Learn From Recent First\u2010Line Treatment Immunotherapy Trials in Non\u2010Small Cell Lung Cancer?","volume":"15","author":"Remon J.","year":"2017","journal-title":"BMC Medicine"},{"issue":"2","key":"e_1_2_12_28_1","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/s41588-018-0312-8","article-title":"Tumor Mutational Load Predicts Survival After Immunotherapy Across Multiple Cancer Types","volume":"51","author":"Samstein R. 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G.","year":"2017","journal-title":"Cancer Cell"},{"issue":"23","key":"e_1_2_12_36_1","doi-asserted-by":"crossref","first-page":"4627","DOI":"10.1182\/blood-2013-02-427641","article-title":"SF3B1 Mutations in Chronic Lymphocytic Leukemia","volume":"121","author":"Wan Y.","year":"2013","journal-title":"Blood"},{"issue":"8","key":"e_1_2_12_37_1","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1158\/2159-8290.CD-20-0555","article-title":"Splicing Patterns in SF3B1\u2010Mutated Uveal Melanoma Generate Shared Immunogenic Tumor\u2010Specific Neoepitopes","volume":"11","author":"Bigot J.","year":"2021","journal-title":"Cancer Discovery"},{"issue":"8","key":"e_1_2_12_38_1","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1002\/cam4.3789","article-title":"Characterization of Genetics in Patients With Mucosal Melanoma Treated With Immune Checkpoint Blockade","volume":"10","author":"Buchbinder E. I.","year":"2021","journal-title":"Cancer Medicine"},{"key":"e_1_2_12_39_1","doi-asserted-by":"crossref","first-page":"10615","DOI":"10.1038\/ncomms10615","article-title":"Cancer\u2010Associated SF3B1 Mutations Affect Alternative Splicing by Promoting Alternative Branchpoint Usage","volume":"7","author":"Alsafadi S.","year":"2016","journal-title":"Nature Communications"},{"issue":"9","key":"e_1_2_12_40_1","doi-asserted-by":"crossref","DOI":"10.3390\/cancers17091403","article-title":"Current Treatment of Uveal Melanoma","volume":"17","author":"Hanratty K.","year":"2025","journal-title":"Cancers (Basel)"},{"issue":"2","key":"e_1_2_12_41_1","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1182\/blood.2019000519","article-title":"Mutational Landscape of the Transcriptome Offers Putative Targets for Immunotherapy of Myeloproliferative Neoplasms","volume":"134","author":"Schischlik F.","year":"2019","journal-title":"Blood"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.72318","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.72318","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.72318","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:59:26Z","timestamp":1790657966000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.72318"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,28]]},"references-count":40,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/cam4.72318"],"URL":"https:\/\/doi.org\/10.1002\/cam4.72318","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,28]]},"assertion":[{"value":"2025-12-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e72318"}}