NK cell therapy in cancer and transplantation

Abstract

NK cells have unique properties including memory. Although initially described as MHC unrestricted killers, NK cells have several families of receptors that directly recognize MHC Inhibitory receptors to protect “self” expressing normal tissue from being killed by NK cells and protecting against autoimmunity. Therefore, for NK cells to kill and produce cytokines they must encounter activating receptor ligands in the context of “missing self” that occurs with malignant transformation. The second property of inhibitory receptors is to educate or license NK cells to acquire function. This is best demonstrated in the mouse and in humans by enhanced function on self inhibitory receptor expressing NK cells when in a host expressing cognate ligate. In contrast, NK cells without inhibitory receptors or with non‐self inhibitory receptors are relatively hyporesponsive. Understanding the biology of NK cells will translate into strategies to manipulate NK cells for therapeutic purposes in cancer and transplantation.