{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:17:07Z","timestamp":1788585427503,"version":"build-2803163510"},"reference-count":34,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>OX40 (TNFRSF4) is a costimulatory T-cell receptor and OX40 agonists are in clinical development, yet its role in small cell lung cancer (SCLC) is still to be characterised. We analysed the discovery cohort (n = 77, 48 events), GSE60052 (n = 79 tumours; 48 with survival), GDSC1+GDSC2 (61 SCLC cell lines, 542 drugs) and human SCLC single-cell atlas (77,143 cells from primary and metastatic sites, 20 donors), using Cox models, FDR-controlled correlation, nested-model comparison and deconvolution. High TNFRSF4 showed a non-significant protective trend (pooled HR = 0.86 per SD, 0.68\u20131.10, p = 0.23); a nominal cutpoint did not survive correction for cutpoint search (p = 0.25). No drug reached FDR &lt; 0.05 among 658 tests, including platinum agents and etoposide. TNFRSF4 tracked immune infiltration (13-gene score \u03c1 = 0.76, p = 3 \u00d7 10\u221216) and was detected in 17.6% of T cells versus 1.03% of malignant cells in all 20 donors. OX40 was enriched in the POU2F3\/SCLC-P subtype (p = 0.033), persisting after immune adjustment (\u03b2 = 1.32, p = 0.011) but not replicating independently (p = 0.10). Adding TNFRSF4 to clinical-plus-immune models provided no meaningful discrimination gain (\u0394C-index \u2264 0.005). Power was limited to HR \u2265 1.50 harmful or HR \u2264 0.67 protective, so the observed trend is undetectable at this size. Bulk OX40 therefore primarily reflects immune infiltration, and its SCLC-P association is a hypothesis for prospective testing.<\/jats:p>","DOI":"10.3390\/ijms27177823","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:48:36Z","timestamp":1788256116000},"page":"7823","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["OX40 (TNFRSF4) Tracks Immune Infiltration in Small Cell Lung Cancer and Shows a Cohort-Specific, Non-Replicated Association with the POU2F3\/SCLC-P Subtype: A Multi-Source In Silico Analysis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1316-0981","authenticated-orcid":false,"given":"Mehmet Turan","family":"\u00d6zer","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Osmaniye Training and Research Hospital, 80010 Osmaniye, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2863-3243","authenticated-orcid":false,"given":"Faruk Recep","family":"\u00d6zalp","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Dokuz Eyl\u00fcl University, 35340 \u0130zmir, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.annonc.2021.03.207","article-title":"Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"32","author":"Dingemans","year":"2021","journal-title":"Ann. 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