Metabolic regulation of NK cell function: implications for immunotherapy

Natural killer (NK) cells are innate immune lymphocytes capable of rapidly responding to tumors and infection without prior sensitization. There is increasing interest and success in harnessing NK cell function for the treatment of disease, in particular cancers. NK cell activation is dependent on integration of signals through cytokine and germline-encoded activating and inhibitory receptors. The availability of metabolic fuels and pathways is required for NK effector functions including proliferation, killing, and production of interferon gamma (IFN-γ). An understanding of NK cell immunometabolism is thus essential for developing immunotherapy approaches that will allow for optimal effector functions in patients. Studies in mice and humans have demonstrated stimulation-dependent metabolic changes that are required for NK cell function. Here we review the most recent findings in NK cell immunometabolism relevant to disease models and translation to therapy of patients.