The Natural Killer–Dendritic Cell Immune Axis in Anti-Cancer Immunity and Immunotherapy

Natural killer (NK) cells and dendritic cells (DCs) are crucial mediators of productive immune responses to infection and disease. NK cells and a subtype of DCs, the type 1 conventional DCs (cDC1s), are individually important for regulating immune responses to cancer in mice and humans. Recent work has found that NK cells and cDC1s engage in intercellular cross-talk integral to initiating and coordinating adaptive immunity to cancer. This NK cell–cDC1 axis has been linked to increased overall survival and responses to anti-PD-1 immunotherapy in metastatic melanoma patients. Here, we review recent findings on the role of NK cells and cDC1s in protective immune responses to cancer and immunotherapy, as well as current therapies targeting this NK cell–cDC1 axis. Further, we explore the concept that intercellular cross-talk between NK cells and cDC1s may be key for many of the positive prognostic associations seen with NK cells and DCs individually. It is clear that increasing our understanding of the NK cell–cDC1 innate immune cell axis will be critical for the generation of novel therapies that can modulate anti-cancer immunity and increase patient responses to common immunotherapies.