Myeloid-Derived Suppressor Cells in Patients with Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance.

Abstract

4890 Background Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of cells of myeloid origin, and include immature macrophages, granulocytes, dendritic cells (DC) and other myeloid cells. In mice, are phenotypically characterized as CD11b+Gr-1+. Humans MDSC have an immature phenotype, including lineage negative (Lin-), CD14-, HLA-DR-, CD15+, CD34+, CD11b+, CD33+, and CD13+ cells. MDSC impair T-cell functions through secretion immunosuppressive cytokines, perturbation of the arginine metabolism by inducible nitric oxide synthase (iNOS), up-regulation of reactive oxygen species (ROS), therefore are considered an important tumor escape mechanism. These cells, also promote tumor-dependent angiogenesis as well as tumor metastasis, and to provide tumor resistance to antiangiogenic drugs. Their accumulation has been described in the peripheral blood of patients affected by breast, lung, renal and neck carcinoma, melanoma, chronic infections, inflammatory diseases, and traumatic stress. We investigate MSDC in patients with multiple myeloma (MM) and monoclonal gammopathy undetermined significance (MGUS) by flow cytometry Methods We studied 22 patients with MM at diagnosis, 20 patients with MGUS, and 10 healthy controls (HC). Results we observed that patients with MGUS showed the same number of MDSC (CD11b+,CD13+,CD34+,CD14-,CD45+) in the peripheral blood compared to HC (1,90±1,03/mmc, p=0,23). On the contrary, patients affected by MM showed a significant increase of MDSC vs HC (6,80±8,79/mmc vs 1,45± 0,98/mmc, p=0,003). Conclusion Our results suggest that these myeloid-derived suppressor cells, through their mechanisms immunesuppressive and proangiogenesis, could be involved in the progression of MGUS towards overt MM. Disclosures No relevant conflicts of interest to declare.

Myeloid‐derived suppressor cells – their role in haemato‐oncological malignancies and other cancers and possible implications for therapy

“…Patients with advanced-stage HL (stages III and IV) had more MDSCs than those with early disease, (stage I and II) (Parrinello et al, 2009b). The same investigators also reported on the levels of MDSCs in 22 patients with multiple myeloma (MM) at diagnosis and in 20 patients with monoclonal gammopathy of undetermined significance (MGUS) using flow-cytometry (Parrinello et al, 2009a). They observed that patients with MGUS showed the same number of MDSCs (CD11b + , CD13 + , CD34 + , CD14 ) , CD45 + ) in the peripheral blood as healthy controls while patients with MM had a significant increase in MDSCs (Parrinello et al, 2009a).…”

“…The same investigators also reported on the levels of MDSCs in 22 patients with multiple myeloma (MM) at diagnosis and in 20 patients with monoclonal gammopathy of undetermined significance (MGUS) using flow-cytometry (Parrinello et al, 2009a). They observed that patients with MGUS showed the same number of MDSCs (CD11b + , CD13 + , CD34 + , CD14 ) , CD45 + ) in the peripheral blood as healthy controls while patients with MM had a significant increase in MDSCs (Parrinello et al, 2009a). Although these results are preliminary, representing only data analysed by flow cytometry, they may indicate that MDSCs could play a role in the progression of MGUS to overt MM via different immunosuppressive and proangiogenic effects.…”

“…Studies related to the role of MDSCs in haemato‐oncological malignancies are still sparse and include mostly heterogeneous groups of patients with both solid and haematological tumours (Diaz‐Montero et al , 2009) or analyses of only small groups of patients (Parrinello et al , 2009a,b; Van Valckenborgh et al , 2009; Wei et al , 2009). From these studies, it is evident that MDSCs are still an open field of research in haemato‐oncology.…”