Fig. 8. Schematic summary.

(Left) In response to flank tumors, tumor-reactive CD8⁺ T cells primed in the iLN up-regulate CD25 and IL-12R, express effector molecules, show signs of conventional exhaustion, and respond to CBT. (Right) In response to lung tumors, however, tumor-reactive CD8⁺ T cells primed in the mLN activate a lung-specific dysfunctional program (T_Ldys), do not up-regulate CD25 and IL-12R, fail to gain effector molecule expression, and do not acquire a conventional T_ex phenotype. CD8⁺ TLdys cells do not respond to CBT. This suggests that differentiation of CD8⁺ T cells into dysfunctional states other than conventional T_ex drives CBT resistance in a subset of T cell–infiltrated NSCLCs. T_eff, effector T cell. Created with Biorender.com.