Natural Killer Cells: the Missing Link in Effective Treatment for High-Grade Serous Ovarian Carcinoma

Opinion statement Ovarian cancer (OC), especially high-grade serous cancer (HGSC), is a highly heterogeneous malignancy with limited options for curative treatment and a high frequency of relapse. Interactions between OC and the immune system may permit immunoediting and immune escape, and current standard of care therapies can influence immune cell infiltration and function within the tumor microenvironment. Natural killer (NK) cells are involved in cancer immunosurveillance and immunoediting and can be activated by therapy, but deliberate approaches to maximize NK cell reactivity for treatment of HGSC are in their infancy. NK cells may be the ideal target for immunotherapy of HGSC. The diverse functions of NK cells, and their established roles in immunosurveillance, make them attractive candidates for more precise and effective HGSC treatment. NK cells' functional capabilities differ because of variation in receptor expression and genetics, with meaningful impacts on their anticancer activity. Studying HGSC:NK cell interactions will define the features that predict the best outcomes for patients with the disease, but the highly diverse nature of HGSC will likely require combination therapies or approaches to simultaneously target multiple, co-existing features of the tumor to avoid tumor escape and relapse. We expect that the ideal therapy will enable NK cell infiltration and activity, reverse immunosuppression within the tumor microenvironment, and enable effector functions against the diverse subpopulations that comprise HGSC.