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Former studies have highlighted RUNX3 as a prognostic factor across several cancer types, but few have studied its cell-type specific expression patterns. We used multiplex immunohistochemistry to assess and quantify cells co-expressing CD3 and RUNX3 in three cohorts consisting of 452 colon adenocarcinoma (COAD), 239 lung adenocarcinoma (LUAD) and 307 lung squamous cell carcinoma (LUSC) patients. Further, we correlated the expression of CD3\/RUNX3 to disease-specific survival and to previously investigated immune markers in these cohorts. We found that a high density of CD3\n                    <jats:sup>+<\/jats:sup>\n                    RUNX3\n                    <jats:sup>+<\/jats:sup>\n                    cells was an independent prognostic factor for disease-specific survival in COAD (HR 0.37, 95% CI 0.21\u20130.64) and LUAD (HR 0.61, 95% CI (0.39\u20130.97), but not in LUSC. Interestingly, RUNX3 expression was positively correlated with CD8 in all cohorts, CD20 in LUAD and FOXP3 in LUSC. Univariate subgroup analyses revealed that COAD patients with high numbers of both CD3\n                    <jats:sup>+<\/jats:sup>\n                    RUNX3\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    cells rarely experienced a DSS event (HR 0.24, 95% CI 0.15\u20130.39). Contrasting previous studies, we did not observe RUNX3 expression in epithelial cells. A high level of CD3\n                    <jats:sup>+<\/jats:sup>\n                    RUNX3\n                    <jats:sup>+<\/jats:sup>\n                    density is an independent prognostic factor in COAD and LUAD, but not in LUSC. In COAD, a subset of patients in stage II\/III with CD3\n                    <jats:sup>+<\/jats:sup>\n                    RUNX3\n                    <jats:sup>+<\/jats:sup>\n                    <jats:sub>high<\/jats:sub>\n                    \/CD8\u2009\n                    <jats:sup>+<\/jats:sup>\n                    \u2009\n                    <jats:sub>high<\/jats:sub>\n                    may be spared adjuvant treatment due to excellent prognosis. However, further studies are needed to confirm and elucidate the protective role of CD3\n                    <jats:sup>+<\/jats:sup>\n                    RUNX3\n                    <jats:sup>+<\/jats:sup>\n                    cells in COAD and LUAD.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-38765-4","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T12:25:51Z","timestamp":1770294351000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CD3+RUNX3+ lymphocyte density; an independent prognostic factor in colon and lung adenocarcinoma but not in lung squamous cell carcinoma"],"prefix":"10.1038","volume":"16","author":[{"given":"Thomas K.","family":"Kilvaer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dagny","family":"F\u00f8rde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erna-Elise","family":"Paulsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona Irene","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Paola","family":"Lombardi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehrdad","family":"Rakaee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hallgeir","family":"Selven","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"Donnem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lill-Tove Rasmussen","family":"Busund","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sigve","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"key":"38765_CR1","first-page":"229","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray, F. et al. 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Transl Oncol. 27, 101568 (2023).","journal-title":"Transl Oncol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-38765-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-38765-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-38765-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T12:37:31Z","timestamp":1771591051000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-38765-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,5]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["38765"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-38765-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,5]]},"assertion":[{"value":"14 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"T.K.K. has received a honorary fee for participation in an advisory board for Sun Pharma, M.R. has received lecture fees from AstraZeneca. All other authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The study was conducted according to the guidelines of the Declaration of Helsinki, and was approved by the Regional Committee for Medical and Health Research Ethics North (REK Nord, protocol IDs: 2011\/2503 and 2011\/2151). The need for informed consent was waived by REK Nord due to the retrospective nature of the study. The reporting of clinicopathological variables, survival data and biomarker expression was conducted in accordance with the REMARK guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"7361"}}