<i>CDKN2A</i> mRNA Over-expression Is Associated With CD8+ T Cell Exclusion and IDO1-Mediated Adaptive Immune Resistance in Gastric Adenocarcinoma.

Background/Aim: over-expression and CD8+ T cell exclusion in gastric adenocarcinoma, but transcriptomic validation and mechanistic characterization remain limited. Materials and Methods: We 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 <-1.0; n=57), Wild-Type (-1.0 ≤ z ≤ +1.0; n=253), and Over-expression (z >+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. Results: =0.73) molecular subtypes reveal prognostic associations. Conclusion: 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.