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CD8\n                    <jats:sup>+<\/jats:sup>\n                    tumor\u2010specific T cells (TSTs) are essential for ICB efficacy, yet it remains unclear which functional states of these cells are associated with therapeutic benefit. To address this, we developed TSTScope, an interpretable deep learning framework that integrates single\u2010cell transcriptomic and T\u2010cell receptor sequencing data to generate unified representations of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell identity. By applying TSTScope to non\u2010small cell lung cancer (NSCLC) datasets, we characterized the gene programs defining tumor specificity and computationally inferred a population of potential TSTs (pTSTs). Our analyses show that clinical response is associated with the functional state of these cells rather than their abundance alone. We derived the major pathological response (MPR) score, a metric capturing this functional potential. In an independent validation cohort, the MPR score was associated with pathological response and recurrence\u2010free survival and provided complementary information to selected response\u2010associated biomarkers. Collectively, TSTScope identifies a distinct functional state of tumor\u2010specific T cells linked to ICB response, providing an interpretable framework for studying receptor\u2010linked T\u2010cell function in immunotherapy cohorts.\n                  <\/jats:p>","DOI":"10.1002\/advs.76983","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T14:11:12Z","timestamp":1785939072000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TSTScope Unifies Single\u2010Cell Multi\u2010Omics to Identify Functional T Cell States Predictive of Immunotherapy Response"],"prefix":"10.1002","volume":"13","author":[{"given":"Shiwei","family":"Cao","sequence":"first","affiliation":[{"name":"School of Life Science and Technology ShanghaiTech University  Shanghai China"},{"name":"Guangzhou National Laboratory  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyu","family":"Cheng","sequence":"additional","affiliation":[{"name":"Guangzhou National Laboratory  Guangzhou China"},{"name":"Multimedia Laboratory (MMLab) The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng\u2010ao","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangzhou National Laboratory  Guangzhou China"},{"name":"Key Laboratory of Systems Health Science of Zhejiang Province School of Life Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxin","family":"Yi","sequence":"additional","affiliation":[{"name":"Guangzhou National Laboratory  Guangzhou China"},{"name":"School of Intelligent Systems Engineering Sun Yat\u2010sen University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajun","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangzhou National Laboratory  Guangzhou China"},{"name":"School of Intelligent Systems Engineering Sun Yat\u2010sen University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyue","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangzhou National Laboratory  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8446-4221","authenticated-orcid":false,"given":"Junwei","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangzhou National Laboratory  Guangzhou China"},{"name":"GMU\u2010GIBH Joint School of Life Sciences The Guangdong\u2010Hong Kong\u2010Macau Joint Laboratory For Cell Fate Regulation and Diseases Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1198-7176","authenticated-orcid":false,"given":"Yixue","family":"Li","sequence":"additional","affiliation":[{"name":"Guangzhou National Laboratory  Guangzhou China"},{"name":"Key Laboratory of Systems Health Science of Zhejiang Province School of Life Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences  Hangzhou China"},{"name":"GMU\u2010GIBH Joint School of Life Sciences The Guangdong\u2010Hong Kong\u2010Macau Joint Laboratory For Cell Fate Regulation and Diseases Guangzhou Medical University  Guangzhou China"},{"name":"School of Life Sciences and Biotechnology Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Institute of Nutrition and Health Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/EDBK_349411"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13988"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201049806\u20109"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010023\u201003129\u2010y"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2024.100553"},{"key":"e_1_2_10_7_1","doi-asserted-by":"crossref","unstructured":"W.Lai Y.Li andO. 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