The therapeutic role of natural killer cells in multiple myeloma

Abstract

Multiple myeloma (MM) is a malignant disease of plasma cells that is also characterized by immune dysregulation. There are several factors that contribute to an immunosuppressive milieu that allows tumor progression, including alterations in natural killer (NK) cells such as a decreased expression of activating receptors. NK cells play an important role in immunosurveillance against cancer. The mainstays of myeloma therapy, such as proteasome inhibitors and immunomodulatory drugs, up-regulate the expression of activating receptors (NKG2D, DNAM-1) on NK cells thereby augmenting their activity against malignant plasma cells. Cellular therapy incorporating NK cells in both the transplant and nontransplant setting offers exciting opportunities for the future. Chimeric antigen receptor (CAR)-transduced-NK cells and bispecific antibodies utilizing NK cells have already been explored in other hematologic malignancies and hold great potential against myeloma. Future clinical studies will help in clarifying the issues related to dose, frequency, long-term safety, and efficacy of NK cell therapy in multiple myeloma.