Abstract
Ovarian cancer represents a leading cause of mortality among gynecologic cancers, with limited therapeutic options for advanced and recurrent disease, highlighting an urgent need for innovative immunotherapies. Natural Killer (NK) cells, functioning as crucial effector cells of the innate immune system, have been identified as promising candidates for ovarian cancer treatment. This review systematically examines the evolving landscape of NK cell-based therapies for ovarian cancer, spanning their preclinical rationale, clinical translation, and innovative combination strategies. Nevertheless, the highly immunosuppressive tumor microenvironment (TME) of ovarian cancer and barriers to tumor infiltration pose significant challenges to their clinical efficacy. Here, we discuss various therapeutic strategies (such as cytokine-based agents, NK cell engagers and chimeric antigen receptor NK cells) designed to enhance NK cell activity, which leverage the unique characteristics of NK cells to complement standard treatments and potentiate combination immunotherapies. Ongoing preclinical and clinical investigations are paramount to converting these advances into efficacious therapies, ultimately revolutionizing the therapeutic paradigm for ovarian cancer.