Targeting NK Cells to Enhance Melanoma Response to Immunotherapies

SIMPLE SUMMARY: NK cells are innate immune cells that form one of the initial responses to infections and cancers. There have been increasing number of studies investigating the anti-tumor effects of NK cells. Immunotherapy targeting NK cell may enhance the therapeutic efficacy of current immunotherapy regimes. Through pro-inflammatory cytokine production, enhancing B cell production of antibodies, facilitate and activate dendritic cells, activate T cells and participating in anti-tumor immunity through the granzyme B pathway and antibody-dependent cellular cytotoxicity, the versatility of NK cells provides an attractive immunotherapy option. This review highlights NK cell biology, NK cell antitumor immunity, NK cell immune evasive mechanisms and novel immunotherapies that aim to target NK cells. ABSTRACT: Natural killer (NK) cells are a key component of an innate immune system. They are important not only in initiating, but also in augmenting adaptive immune responses. NK cell activation is mediated by a carefully orchestrated balance between the signals from inhibitory and activating NK cell receptors. NK cells are potent producers of proinflammatory cytokines and are also able to elicit strong antitumor responses through secretion of perforin and granzyme B. Tumors can develop many mechanisms to evade NK cell antitumor responses, such as upregulating ligands for inhibitory receptors, secreting anti-inflammatory cytokines and recruiting immunosuppressive cells. Enhancing NK cell responses will likely augment the effectiveness of immunotherapies, and strategies to accomplish this are currently being evaluated in clinical trials. A comprehensive understanding of NK cell biology will likely provide additional opportunities to further leverage the antitumor effects of NK cells. In this review, we therefore sought to highlight NK cell biology, tumor evasion of NK cells and clinical trials that target NK cells.