Abstract
Myeloid-derived suppressor cells (MDSCs) are heterogeneous populations of immature myeloid cells with immunosuppressive effects that have prognostic potential in patients with malignancies; however, survival analysis studies are sparse. In this study, the prognostic implication of MDSCs was investigated in peripheral blood (PB) and bone marrow (BM) samples from 81 patients with plasma cell myeloma at diagnosis. MDSCs were quantified as monocytic MDSCs (mMDSCs) (CD11b+HLA-DR−/lowCD14+) and granulocytic MDSCs with neutrophils (gMDSCs-N) (CD11b+HLA-DR−/lowCD14−CD33+CD15+). Serum creatinine and lactate dehydrogenase levels showed a moderate correlation with all MDSC types, except BM-gMDSCs-N; mMDSCs correlated with serum β2-microglobulin level, and PB-mMDSCs showed an inverse correlation with hemoglobin. PB-mMDSC levels were significantly higher in patients with progressive disease than those in patients at diagnosis and complete response. BM-mMDSC levels in patients with progressive disease were also higher than those in patients at diagnosis. Patients with high mMDSCs showed significantly poorer prognosis than patients with low mMDSCs. Multivariate analysis showed high PB-mMDSCs (≥0.3%) as a significant adverse prognostic marker for overall survival. This study demonstrated the independent adverse prognostic impact of PB-mMDSCs in patients with myeloma. PB-mMDSC measurement using whole blood is readily accessible in clinical laboratories, and may be used as a prognostic marker in clinical practice.
Highlights
Myeloid-derived suppressor cells (MDSCs) are heterogeneous populations of immature myeloid cells that have the ability to regulate immune responses [1]
Studies exploring the role of MDSCs in hematological malignancies, including plasma cell myeloma (PCM) [8,9], have reported that MDSC levels are increased in peripheral blood (PB) of patients with active PCM compared with those in healthy individuals, and the immune-suppressive and tumor-promoting effects of MDSCs in the PCM microenvironment have been confirmed [10,11]
MDSCs are immature myeloid cells that have defective differentiation, that contribute to tumor immune tolerance, and that promote tumor progression in several malignancies [5,8,13]
Summary
Myeloid-derived suppressor cells (MDSCs) are heterogeneous populations of immature myeloid cells that have the ability to regulate immune responses [1]. Their numbers are elevated in chronic pathological conditions, such as infection, inflammation, and cancer [2,3]. Studies exploring the role of MDSCs in hematological malignancies, including plasma cell myeloma (PCM) [8,9], have reported that MDSC levels are increased in peripheral blood (PB) of patients with active PCM compared with those in healthy individuals, and the immune-suppressive and tumor-promoting effects of MDSCs in the PCM microenvironment have been confirmed [10,11]. Clinical studies based on MDSCs in PCM are sparse, and so far, only one study has reported the adverse prognostic impact of monocytic MDSCs (mMDSCs) in the PB of patients with PCM at the pre-autologous stem cell transplantation phase [12]
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