Natural killer cell immunotherapies against cancer: checkpoint inhibitors and more

•NK cell cytotoxicity is regulated by an array of activating and inhibitory receptors.•NK cell infiltration is a favorable prognostic factor in various solid tumors.•mAbs against inhibitory receptors enhance NK cell functions in vivo.

After many years of research, recent advances have shed new light on the role of the immune system in advanced-stage cancer. Various types of immune cells may be useful for therapeutic purposes, along with chemical molecules and engineered monoclonal antibodies. The immune effectors suitable for manipulation for adoptive transfer or drug targeting in vivo include natural killer (NK) cells. These cells are of particular interest because they are tightly regulated by an array of inhibitory and activating receptors, enabling them to kill tumor cells while sparing normal cells. New therapeutic antibodies blocking the interactions of inhibitory receptors (immune checkpoint inhibitors, ICI) with their ligands have been developed and can potentiate NK cell functions in vivo.