NK cells and CD8 T cells in cancer immunotherapy: Similar functions by different mechanisms

Abstract NK cells and CD8 T cells are cytotoxic lymphocytes that have critical protective roles against pathogens and cancers. NK cells are conventionally regarded as rapid-acting cells of the innate branch of the immune system, while CD8 T cells act later in infections and in long-term memory responses. Both cells have similar cytotoxic pathways and respond to the same cytokines. We discuss how NK cells and T cells break the mold of innate and adaptive immunity with evidence that NK cells exhibit memory-like responses and memory bystander T cells rapidly respond to cytokine signals in heterologous challenges. A great deal is still unknown about coregulation of NK cells and T cells and the factors that are necessary for preserving long-term memory responses; however, light is being shed on the importance of inhibitory receptors for preventing cells from activation-induced cell death (AICD). Above all, there is a fine balance between having a protective immune response at the time of challenge and preventing immune-mediated pathology, while also generating long-lived memory cell populations with enhanced functions for the future. There are many exciting new therapeutic approaches aimed at utilizing NK cells and T cells to their full advantage for potent and long-term antitumor responses.