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This reflects molecular heterogeneity of GC, as defined by The Cancer Genome Atlas (TCGA) into four subtypes: Epstein\u2013Barr virus (EBV)\u2010positive, microsatellite instability (MSI), chromosomal instability (CIN), and genomically stable (GS), each with distinct immune features. We aimed to characterize distribution, clinical relevance, and immune associations of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration within this molecular framework. TCGA (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009336) and Zhongshan Hospital (ZSHS,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009455) cohorts were analyzed. CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration and immune features were compared across TCGA subtypes. Prognostic and predictive significance of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells was evaluated in ZSHS cohort. CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration was elevated in the EBV\u2010positive and MSI subtypes (ZSHS:\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.026; TCGA:\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). In ZSHS cohort, high CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration was associated with better overall survival (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.040), particularly in the EBV\u2010positive (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.036) and CIN (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.065) subtypes, but not in MSI (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.440) or GS (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.860). Notably, low CD8\n                    <jats:sup>+<\/jats:sup>\n                    T infiltration predicted superior response to adjuvant chemotherapy in MSI patients (HR\u2009=\u20090.210,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.022). Immune profiling revealed associations of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells with antigen presentation in EBV\u2010positive, tertiary lymphoid structure signatures in CIN, and podoplanin+ cells in GS tumors, instead of neoantigen burden in MSI or pan\u2010fibroblast TGF\u03b2 response signature in GS. CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration demonstrates subtype\u2010specific prognostic and therapeutic significance in GC\u2014beneficial in EBV\u2010positive and CIN tumors, and predictive of chemotherapy response in MSI with low infiltration, which accompanied by divergent immune features, reflecting heterogeneous immunological landscape of GC.\n                  <\/jats:p>","DOI":"10.1111\/cas.70366","type":"journal-article","created":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T06:16:23Z","timestamp":1774073783000},"page":"1434-1445","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>CD8<\/scp>\n                    <sup>+<\/sup>\n                    T Cell Infiltration Elicits Molecular Subtype\u2010Biased Clinical Outcomes in Gastric Cancer Patients"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9831-4846","authenticated-orcid":false,"given":"Zhen","family":"Ling","sequence":"first","affiliation":[{"name":"National Health Commission Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7251-4225","authenticated-orcid":false,"given":"Jieti","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endoscopy, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6942-0749","authenticated-orcid":false,"given":"Yun","family":"Gu","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences Fudan University  Shanghai China"},{"name":"Department of Gastrointestinal Surgery, Shanghai Sixth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5637-8415","authenticated-orcid":false,"given":"Ziqiu","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8337-0247","authenticated-orcid":false,"given":"Fei","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Oncology, Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2800-0208","authenticated-orcid":false,"given":"Chao","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Acute Care Surgery, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7371-4133","authenticated-orcid":false,"given":"Hongyong","family":"He","sequence":"additional","affiliation":[{"name":"Department of Acute Care Surgery, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4013-3281","authenticated-orcid":false,"given":"Ruochen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Acute Care Surgery, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1792-9209","authenticated-orcid":false,"given":"Hao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7431-9063","authenticated-orcid":false,"given":"Jiejie","family":"Xu","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-020-0265-5"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.01.018"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13480"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0101-z"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens13090728"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.01124"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.11.016"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242316961"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-01048-4"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.06.025"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.01.009"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27782"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0812-9"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cllc.2022.04.001"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14204974"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.02030"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30789-X"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0734-6"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-020-0285-7"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604738"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-310839"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.02.016"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-019-0291-z"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.04.011"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-022-01939-8"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2021.1915560"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyab026"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000756"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2014.388"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2020.1845038"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-025-06291-y"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00549-2"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac9935"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111878"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16112062"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.21037\/jgo-24-345"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-025-03002-8"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.16057"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1500596"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001779"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-01048-4"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-0813-y"},{"issue":"9","key":"e_1_2_12_44_1","first-page":"97","article-title":"Microsatellite Instability in Colorectal cancer","volume":"89","author":"De\u2019 Angelis G. L.","year":"2018","journal-title":"Acta Bio\u2010Medica"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1136\/esmoopen-2018-000326"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1177\/17588359241231259"},{"issue":"4","key":"e_1_2_12_47_1","first-page":"1178","article-title":"Adjuvant Chemotherapy in Microsatellite Instability\u2010High Gastric Cancer","volume":"52","author":"Kim J. 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