{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:20:05Z","timestamp":1785799205287,"version":"3.56.0"},"reference-count":0,"publisher":"International Institute of Anticancer Research","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CDP"],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:p>Background\/Aim: \nCellular senescence, mediated by CDKN2A-encoded p16INK4a, generates a senescence-associated secretory phenotype (SASP) that may promote immune evasion in solid tumors. Recent immunohistochemical studies have identified associations between p16INK4a over-expression and CD8+ T cell exclusion in gastric adenocarcinoma, but transcriptomic validation and mechanistic characterization remain limited.\nMaterials and Methods: \nWe analyzed 386 gastric adenocarcinoma samples from The Cancer Genome Atlas (TCGA-STAD) cohort, stratifying patients by CDKN2A mRNA expression using z-score thresholds: Loss (z &lt;\u22121.0; n=57), Wild-Type (\u22121.0 \u2264 z \u2264 +1.0; n=253), and Over-expression (z &gt;+1.0; n=76). Immune cell infiltration was estimated with quanTIseq deconvolution. SASP factor expression (IDO1, TGFB1, NT5E) and correlations with immune populations were assessed using Kruskal-Wallis tests, pairwise Wilcoxon rank-sum tests, and Spearman correlation analyses.\nResults: \nCDKN2A over-expression was significantly associated with CD8+ T cell depletion (p=0.024) and IDO1 up-regulation (p=0.015) compared to wild-type tumors, validating prior immunohistochemical findings. However, TGFB1 (p=0.56) and NT5E (p=0.75) showed no significant differential expression. Paradoxically, IDO1 correlated positively with CD8+ T cell infiltration, as did TGFB1, suggesting reactive up-regulation rather than primary exclusion. Overall survival did not differ significantly across expression groups (p=0.3), nor did stratification by chromosomal instability (CIN p=0.76) or microsatellite instability (MSI p=0.73) molecular subtypes reveal prognostic associations.\nConclusion: \nThis transcriptomic analysis confirms the association between CDKN2A over-expression and an immunosuppressive microenvironment characterized by CD8+ T cell depletion and IDO1 up-regulation. The strong positive correlation between IDO1 and CD8+ T cells supports an adaptive immune resistance model, wherein IDO1 is induced via interferon-gamma signaling as a reactive checkpoint rather than functioning as a primary T cell exclusion factor. These findings suggest that CDKN2A-over-expressing gastric adenocarcinomas may benefit from combination immunotherapy strategies incorporating IDO1 inhibition.<\/jats:p>","DOI":"10.21873\/cdp.10564","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T14:51:52Z","timestamp":1783349512000},"page":"639-648","source":"Crossref","is-referenced-by-count":1,"title":["CDKN2A mRNA Over-expression Is Associated With CD8+ T Cell Exclusion and IDO1-Mediated Adaptive Immune Resistance in Gastric Adenocarcinoma"],"prefix":"10.21873","volume":"6","author":[{"given":"STEVEN","family":"LEHRER","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PETER","family":"RHEINSTEIN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"9336","published-online":{"date-parts":[[2026,7,1]]},"container-title":["Cancer Diagnosis &amp; Prognosis"],"original-title":[],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T14:51:54Z","timestamp":1783349514000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cancerdiagnosisprognosis.org\/article\/626\/cdkn2a-mrna-over-expression-is-associated-with-cd8-t-cell-exclusion-and-ido1-mediated-adaptive-immune-resistance-in-gastric-adenocarcinoma"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":0,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,7,1]]},"published-print":{"date-parts":[[2026,7,1]]}},"URL":"https:\/\/doi.org\/10.21873\/cdp.10564","relation":{},"ISSN":["2732-7787"],"issn-type":[{"value":"2732-7787","type":"print"}],"subject":[],"published":{"date-parts":[[2026,7,1]]}}}