Harnessing NK Cell Memory for Cancer Immunotherapy

Due to their ability to kill cancer cells and produce proinflammatory cytokines, natural killer (NK) cells have long been of clinical interest for their antitumor properties. The recent discovery of NK cell memory demonstrates that NK cell functions, and potentially antitumor responses, can be enhanced long term. Following nonspecific activation with the cytokines IL-12, IL-16, and IL-18 or in response to antigens or cytomegalovirus (CMV), human and mouse NK cells exhibit stable, enhanced functional responses with phenotypic and molecular changes. Here we review mechanisms driving the differentiation of NK cell memory-like properties, evidence for antitumor activity, and the challenges and opportunities in harnessing memory-like NK cells for cancer immunotherapy.