{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:49:20Z","timestamp":1792043360121,"version":"4.4.0"},"reference-count":27,"publisher":"Korean Cancer Association","issue":"4","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100002551","name":"Seoul National University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002551","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["e-crt.org"],"crossmark-restriction":true},"short-container-title":["Cancer Res Treat"],"published-print":{"date-parts":[[2026,10,15]]},"abstract":"PurposeAs immunotherapy has become essential in the treatment of gastric cancer (GC), there has been growing interest in T-cells, which play a key role in immunotherapy. In this study, we evaluated the impact of T-cell subsets on immune responsiveness to immune checkpoint inhibitors (ICIs) in GC using multiplex immunohistochemistry (mIHC).Materials and MethodsEighty-four GC patients treated with ICIs were enrolled, and we repeated the staining-scanning-stripping procedure nine times to assess different kinds of T-cells or cell-surface immune checkpoints in a single tissue section.ResultsThe proportions of patients with microsatellite instability (MSI)\u2013high, Epstein-Barr virus (EBV), and non-MSI\/non-EBV were 8.3%, 3.6%, and 88.1%. A high cytotoxic T-cell (T<sub>cyto<\/sub>) density was related to longer overall survival (OS). GC with a high ratio of T<sub>cyto<\/sub>\/total T-cells (T<sub>total<\/sub>) and a low ratio of regulatory T-cells (T<sub>reg<\/sub>)\/T<sub>total<\/sub> showed better OS. A high density of programmed death-1 (PD-1)\u2013 or TIM-3\u2013expressing T<sub>cyto<\/sub> was also associated with longer OS than a low density of those. Among memory T-cells (T<sub>mem<\/sub>) subsets, GC with a high ratio of memory T<sub>cyto<\/sub>\/T<sub>mem<\/sub> and a low ratio of memory T<sub>reg<\/sub>\/T<sub>mem<\/sub> showed prolonged OS. Better tumor responses were observed in GC with a high ratio of T<sub>cyto<\/sub>\/T<sub>total<\/sub> and memory T<sub>cyto<\/sub>\/T<sub>mem<\/sub>.ConclusionT-cell subsets within the tumor microenvironment were associated with the clinical efficacy of ICIs in GC. PD-1\u2013 or TIM-3\u2013expressing T-cells were also associated with response to ICIs, while T<sub>mem<\/sub> subsets were associated with survival. mIHC is a feasible method for evaluating T-cell subsets in archival gastric tumor tissue.<\/jats:p>","DOI":"10.4143\/crt.2025.458","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T02:10:48Z","timestamp":1757383848000},"page":"1298-1309","update-policy":"https:\/\/doi.org\/10.4143\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Analysis of T-Cell Subsets Using Multiplex Immunohistochemistry and Clinical Outcomes of Immune Checkpoint Inhibitors in Advanced Gastric Cancer Patients"],"prefix":"10.4143","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3930-6766","authenticated-orcid":true,"given":"Tae-Yong","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea"},{"name":"Cancer 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Seung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology, Seoul National University Hospital, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1663-9901","authenticated-orcid":true,"given":"Do-Youn","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea"},{"name":"Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea"},{"name":"Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, 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