Figure 5.

Recent therapeutic approaches to enhance natural killer (NK) cytotoxicity against multiple myeloma (MM). This schematic shows how various therapeutic agents modulate NK cell-mediated cytotoxicity to target myeloma cells. Suppressive immune cells as well as bone marrow stromal cells (BMSCs) inside the tumor microenvironment are negative regulators of NK cell activation. The MM cells themselves develop several strategies to evade NK-cell-mediated killing. New immune modulators, including immunomodulatory drugs (iMiDs), immune checkpoint inhibitors, such as anti-programmed cell death 1 (PD-1)/PD-L1, anti-NKG2A, anti-TIGIT blocking antibodies, and proteasome inhibitors, target and suppress immunosuppressive factors in the MM microenvironment and enhance the cytotoxic effect of NK cells to kill MM cells. In addition, the antibodies used to treat MM, such as elotuzumab and daratumumab, induce NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). TIGIT, T cell immunoreceptor with Ig and ITIM domains; CD16, cluster of differentiation 16; NKG2A, natural killer G2A; MDSC, myeloid-derived suppressor cell; MHC, major histocompatibility complex.