GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE339nnn/GSE339309/primary200OKTranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE339309GEOGSEfalseThymic age and peripheral residence time determine anti-tumor competence of CD8+ T cellsThe developmental timing of T cell generation imprints durable functional programs, yet how this shapes anti-tumor immunity remains unclear. Here, we combine genetic fate mapping with functional assays to dissect how thymic age and peripheral residency regulate CD8⁺ T cell behaviour within the same host. We find that, compared with adulthood-derived CD8⁺ T cells, the adolescent-derived counterparts consistently exhibit enhanced tumor infiltration, increased effector cytokine production, and superior proliferative fitness. Transcriptomic and phenotypic profiling identify a CXCR3⁺IL-18Rα⁺ subset preferentially enriched among adolescent-derived T cells that shares core virtual memory-like features and displays elevated cytotoxic potential. Mechanistically, thymic origin timing and time spent in the periphery independently regulate the abundance and activity of this subset, revealing a two-tier control comprising developmental bias and post-thymic remodelling. Functionally, CXCR3⁺IL-18Rα⁺ CD8⁺ T cells mediate potent tumor killing and confer robust therapeutic benefit in adoptive transfer models. Together, these findings establish developmental imprinting as an important determinant of CD8⁺ T cell heterogeneity and identify CXCR3⁺IL-18Rα⁺ CD8⁺ T cells as key effectors for anti-tumor immunity.2026/09/01GSE339309GSM9893329GSM9893327GSM9893328GSM9893325GSM9893326GSM9893323GSM9893324GSM989332230172339309Mus musculus