Myeloid-Derived Suppressor Cells (MDSCs) Suppress T-Cell Proliferation Less Than Mature Neutrophils in Blood and Bone Marrow From Multiple Myeloma Patients.

Multiple myeloma (MM) is the second most common hematological malignancy, characterized by a clonal expansion of malignant plasma cells in bone marrow. Monoclonal gammopathy of undetermined significance (MGUS) is the premalignant condition of MM. The tumor microenvironment is thought to influence the progression from premalignant conditions. Myeloid-derived suppressor cells (MDSCs) are a heterogenous group of different cellular subsets with myeloid origin, characterized by their ability to inhibit T-cell responses. MDSC are thought to play an important immunoregulatory role in different diseases, and in many cancers their levels seem to correlate with a poor prognosis. There are three different subsets, the neutrophil-like polymorphonuclear (PMN)-MDSC, the monocyte-like (M)-MDSC, and the immature early (e)MDSC. In this study, we investigate the levels and functions of all MDSC subsets in the bone marrow of both MGUS and MM patients and compare it to blood MDSC. We found that MDSC levels are not increased in neither the blood nor bone marrow of MGUS or MM patients, and they lack strong T-cell suppressive abilities. Blood PMN-MDSC seems to have a small inhibitory effect, but mature neutrophils were more suppressive. Interestingly, eMDSC levels were decreased in the blood of MM patients. Our data indicate that MDSC are not key players in the pathogenesis of MM, but that mature neutrophils may be more important as they have a stronger immunoregulatory effect.