Interleukins 15 and 18 synergistically prime the antitumor function of natural killer cells through noncanonical activation of mTORC1
Natural killer (NK) cells have antitumor activity that is primed by IL-15 and IL-18, components of a cytokine cocktail used in NK cell–based cancer immunotherapy. Fallone et al. found that IL-15 and IL-18 synergized to activate the complex mTORC1, which resulted in increased proliferation and function of both mouse and human NK cells. IL-15 and IL-18 stimulated mTORC1 activity through distinct pathways not previously implicated in its regulation. The combination of IL-15 and IL-18 improved the survival of mice engrafted with tumor cells, suggesting a therapeutic strategy to enhance the efficacy of NK cell–based cancer immunotherapy