Targeting myeloid-derived suppressor cells to enhance natural killer cell-based immunotherapy

Myeloid-derived suppressor cells (MDSCs) are immune cells of the myeloid lineage that progressively accumulate in tumors and play an important role in promoting tumor growth. MDSCs interact with other immune cells present in the tumor microenvironment (TME) and utilize multiple mechanisms to promote immunosuppression. On the other hand, natural killer (NK) cells are cytotoxic cells of the innate immune system and work as one of the first lines of defense against tumors. However, the role of MDSCs in regulating or suppressing NK cells within the TME is poorly understood. This review discusses MDSC-associated immunosuppression, the mechanisms regulating communication between MDSCs and NK cells in the tumor microenvironment, and how MDSC may impact NK-cell-based immunotherapies. We also explore various strategies to increase NK cell cytotoxicity by blocking MDSC-mediated immunosuppression with the goal of enhancing cell based anti-cancer therapeutics.