The NK cell–cancer cycle: advances and new challenges in NK cell–based immunotherapies

Natural killer (NK) cells belong to the innate immune system and contribute to protecting the host through killing of infected, foreign, stressed or transformed cells. Additionally, via cellular cross-talk, NK cells orchestrate antitumor immune responses. Hence, significant efforts have been undertaken to exploit the therapeutic properties of NK cells in cancer. Current strategies in preclinical and clinical development include adoptive transfer therapies, direct stimulation, recruitment of NK cells into the tumor microenvironment (TME), blockade of inhibitory receptors that limit NK cell functions, and therapeutic modulation of the TME to enhance antitumor NK cell function. In this Review, we introduce the NK cell–cancer cycle to highlight recent advances in NK cell biology and to discuss the progress and problems of NK cell–based cancer immunotherapies. In this Review, Smyth and colleagues provide an overview of recent advances in NK cell biology and discuss the progress and problems of NK cell–based cancer immunotherapies.