FIGURE 1.

The activating and inhibitory receptor signaling regulates NK cell activation. Cells undergoing stress such as tumor cells lose their MHC class I molecules, ligands for KIR inhibitory receptors on NK cells. At the same time, they acquire stress-associated molecules which act as ligands for the activating receptors NKG2D and DNAM1. Thus, the lack of inhibitory signaling coupled with induction of activating signaling shifts the balance toward NK cell activation, leading to killing of cancer cells. During tumor progression, interaction of immune checkpoint receptors with their cognate ligands diminishes NK cell cytotoxic potential and prevent NK anti-tumor functions.