Thymic age and peripheral residence time determine anti-tumor competence of CD8+ T cells

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.