Tumor-resident CD8+ T-cell: the Critical Catalyst in IL-12-mediated Reversal of Tumor Immune Suppression

Tumor-resident T cells display a functionally impaired effector/memory (Tem) phenotype. Sustained intratumoral administration of IL-12, on the other hand, can restore cytolytic function to pre-existing CD8+ Tem, resulting in effective tumor kill. Whereas cytotoxic T lymphocytes (CTL) are generally assumed to mediate tumor regression via direct tumor cytotoxicity, recent work revealed that activated CD8+ Tem mobilize a systemic, multi-component effector cascade that includes both innate and adaptive immune mechanisms. Here we summarize these mechanisms, review how tumor-resident CD8+ Tem orchestrate this cascade and discuss the potential clinical implications of these findings.