Myeloid-derived suppressor cells in multiple myeloma: mechanistic insights and therapeutic implications

Multiple myeloma (MM) is an incurable malignancy and ranks as the second most common hematological cancer in western countries. Relapsed disease is common in MM patients, and is largely influenced by the establishment of an immunosuppressive tumor microenvironment (TME) and concomitant systemic immune impairment. Myeloid-derived suppressor cells (MDSCs) are crucial regulators of immune homeostasis and response in various pathological states, including cancer. Within the TME, MDSCs and tumor cells engage in bidirectional crosstalk through both direct and indirect mechanisms, collectively driving immune evasion and tumor progression. As a principal immunosuppressive population within the MM milieu, MDSCs play a central role in the immunoregulation of MM. Although immunotherapy has emerged as a pivotal treatment modality for MM, MDSCs, the key constituents of the TME, constitute a major source of resistance to such therapies. This review elucidates the mechanisms governing MDSCs interactions within the myeloma TME, discusses potential therapeutic strategies targeting MDSCs, and outlines a rational framework for integrating MDSC-directed approaches with current MM therapies and immunotherapy.