Role of NK Cells in Progression and Treatment of Multiple Myeloma

Multiple myeloma (MM) is a haematological malignancy originating from terminally differentiated B cells, resulting in significant morbidity and mortality. Currently, MM is regarded as an incurable disease, often exhibiting a relapse-remitting pattern that necessitates multiple lines of therapy. It is now well-established that ineffective immunosurveillance plays a critical role in the progression of MM. Consequently, strategies that redirect immune effector cells against MM have emerged as effective treatment modalities, particularly in cases where standard care therapies fail. T cell-based immunotherapy has gained considerable attention in ongoing clinical trials; however, natural killer (NK) cells, known for their ability to execute cytotoxicity against infected and malignant cells with precision, may offer complementary therapeutic advantages over T cells and possess untapped therapeutic potential. This review seeks to introduce readers to the significance of NK cell-mediated immunosurveillance in the context of MM, explore the potential benefits of redirecting NK cells against MM, and illustrate how current treatment strategies are often reliant on the functionality of NK cells. Most importantly, new promising mechanisms of harnessing NK cell-based immunity against MM are reviewed and put into a clinical perspective to highlight their implications for patient treatment and outcomes.