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.
Egilmez
Nejat K
NK
Department of Microbiology and Immunology, School of Medicine and Biomedical Sciences, University at Buffalo, 138 Farber Hall, 3435 Main Street, Buffalo, NY 14214, USA. negilmez@buffalo.edu
Kilinc
Mehmet O
MO
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007156:Immunologic Memory; D007167:Immunotherapy / Q000379:methods; D018664:Interleukin-12 / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D019139:Tumor Escape
D018664:Interleukin-12