Harnessing Natural Killer Cells in Cancer Immunotherapy: A Review of Mechanisms and Novel Therapies

SIMPLE SUMMARY: Cancer immunotherapy has mostly focused on harnessing adaptive immunity to promote the destruction of neoplastic cells by B and T lymphocytes. We are now increasingly recognizing the important role of the innate immune system in the body’s response to neoplastic cells, providing an opportunity for the development of innovative cancer treatments. Specifically, emerging therapies targeting natural killer (NK) cells, which are integral to the innate immune response, are being investigated for the treatment of various tumor types. Successful efforts would pave the way for entirely new immunotherapeutic strategies in cancer treatment, with numerous possible targets. ABSTRACT: Natural killer (NK) cells are lymphocytes that are integral to the body’s innate immunity, resulting in a rapid immune response to stressed or infected cells in an antigen-independent manner. The innate immune system plays an important role in the recognition of tumor-derived stress-related factors and is critical to subsequent adaptive immune responses against tumor antigens. The aim of this review is to discuss mechanisms by which tumor cells evade NK cells and to outline strategies that harness NK cells for cancer immunotherapy. We discuss strategies to relieve the exhausted state of NK cells, recent therapies focused on targeting NK-cell-specific activating and inhibitory receptors, the use of cytokines IL-2 and IL-15 to stimulate autologous or allogeneic NK cells, and ongoing trials exploring the use of genetically modified NK cells and chimeric antigen-receptor-modified NK (CAR-NK) cells.