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In this study, we stratified the immunotypes of tongue squamous cell carcinoma (TSCC) based on the results of comprehensive immune profiling.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We enrolled 87 therapy-na\u00efve TSCC and 17 ICI-treated TSCC patients who underwent glossectomy without any other prior therapy. Comprehensive immune profile analyses employed multiplex immunofluorescence and tissue imaging.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Based on the hierarchies of 58 immune parameters and the spatial distances between cytotoxic T lymphocytes (CTL) and tumor cells, we stratified five immunotypes: Immunoactive type I, border type II, immunosuppressed type III, immunoisolating type IV, and immunodesert type V. The type I frequency was only 16%. Most TSCCs (~\u200970%) were of types III\u2013V. The CTL density (CTL-D) was closely correlated with the PD-L1<jats:sup>+<\/jats:sup> pan-macrophages (panM)-D, and the panM-D closely correlated with the PD-1<jats:sup>+<\/jats:sup> CTL-D. This indicated that PD-1 and PD-L1 expression required macrophages and CTL recruitment in the tumor microenvironment. No ICI-treated TSCC patients, all of whom were recurrent\/metastatic cases, were of the type I immunotype, and almost half (47.0%) were of the immunodesert type V. Most cases exhibited an imbalance between T-cell PD-1 and macrophage PD-L1 expression.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>We defined five TSCC-specific immunotypes based on the results of comprehensive immune profiling analyses. Immunoactive type, which would be sensitive to ICI monotherapy, was rare, and most TSCC cases exhibited immune-regulated immunotypes. Immunotype-based personalized treatments are required to improve clinical outcomes.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00262-025-03982-9","type":"journal-article","created":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T15:22:32Z","timestamp":1740842552000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Stratification of the immunotypes of tongue squamous cell carcinoma to improve prognosis and the response to immune checkpoint inhibitors"],"prefix":"10.1007","volume":"74","author":[{"given":"Yuya","family":"Su","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Ouchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pissacha","family":"Daroonpan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miwako","family":"Hamagaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tohru","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noji","family":"Rika","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoto","family":"Nishii","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumihiko","family":"Tsushima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihito","family":"Kano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Asakage","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Noguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Harada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miyuki","family":"Azuma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,3,1]]},"reference":[{"key":"3982_CR1","doi-asserted-by":"publisher","first-page":"2188","DOI":"10.1016\/j.immuni.2023.09.011","volume":"56","author":"I Mellman","year":"2023","unstructured":"Mellman I, Chen DS, Powles T, Turley SJ (2023) The cancer-immunity cycle: indication, genotype, and immunotype. 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