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Adv."],"published-print":{"date-parts":[[2026,7,17]]},"abstract":"<jats:p>\n                    How cancer-associated fibroblasts (CAFs) dictate CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell dysfunction during lung cancer remains unclear. Through single-cell analysis of 84 human NSCLC samples, we identified insulin-like growth factor 2 (IGF2) as a key immunosuppressive factor in a specific CAF subset. IGF2\n                    <jats:sup>+<\/jats:sup>\n                    CAF infiltration correlated with CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell dysfunction. Fibroblast-specific IGF2 knockout enhanced antigen presentation cell-autonomously via major histocompatibility complex class I (MHC-I), boosting CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell effector function, tumor suppression, survival, and PD-1 blockade synergy. Mechanistically, IGF2 sustained MYC signaling to up-regulate DNA methyltransferase 1 (DNMT1), which methylated the STAT1 promoter, epigenetically silencing STAT1. This impaired MHC-I presentation and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell activation. Clinically, high IGF2 levels associated with reduced CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell cytotoxicity and poor outcomes. An IGF2\n                    <jats:sup>+<\/jats:sup>\n                    fibroblast signature predicted worse response to immunotherapy in multiple cohorts. Our findings establish IGF2 as a central regulator of CAF-mediated immunosuppression and a stromal target for enhancing immunotherapy in lung cancer.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aee5738","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T17:58:48Z","timestamp":1784311128000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Fibroblast-specific ablation of MHC-I antigen presentation via the IGF2 axis cripples CD8\n                    <sup>+<\/sup>\n                    T cell surveillance in lung cancer"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4091-4455","authenticated-orcid":true,"given":"Daqiang","family":"Song","sequence":"first","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Women and Children\u2019s Hospital of Chongqing Medical University, Chongqing, China."},{"name":"Department of Breast and Thyroid Surgery, Chongqing Health Center for Women and Children, Chongqing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1058-6407","authenticated-orcid":true,"given":"Hongtao","family":"Tie","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9025-624X","authenticated-orcid":true,"given":"Qianxue","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guomin","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Chongqing Key Laboratory of 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