Reactivation of natural killer cells with monoclonal antibodies in the microenvironment of malignant neoplasms

Natural killer cells are critical players in the antitumor immune response due to their ability to destroy target cells through cytotoxic activity and other means. However, this response is inhibited in the tumor microenvironment, where a crippling hypoxic environment and several inhibitory molecules bind to NK cells to trigger an anergic state. Inhibitory receptors such as PD-1, NK2GA, KIR, TIGIT, and LAG-3 have been associated with inhibition of NK cells in multiple cancer types. Binding to these receptors leads to loss of cytotoxicity, lower proliferation and metabolic rates, and even apoptosis. While these receptors are important for avoiding auto-immunity, in a pathological setting like malignant neoplasms they are disadvantageous for the individual's immune system to combat cancer cells. The use of monoclonal antibodies to block these receptors contributes to cancer therapy by preventing the inhibition of NK cells. In this review, the impact of NK cell inhibition and activation on cancer therapy was summarized and an overview of the blockade of inhibitory pathways by monoclonal antibodies was provided.