title: Tumor-induced CD14+HLA-DR (-/low) myeloid-derived suppressor cells correlate with tumor progression and outcome of therapy in multiple myeloma patients.
abstract: Myeloid-derived suppressor cells (MDSCs) are heterogeneous, immature, myeloid progenitor cells, which suppress immune responses against tumors. CD14(+)HLA-DR(-/low) monocytic MDSCs (M-MDSC) are increased in patients suffering from multiple myeloma (MM). However, the frequency and function of M-MDSCs with the relationship between the tumor development and outcome of therapy in MM remain unclear. In this study, we analyzed the changes in M-MDSCs in newly diagnosed, relapsed and remission MM patients. In addition, we also assessed the response of M-MDSCs in MM patients treated with a bortezomib-based therapy as well as the impact of bortezomib on the modulation of M-MDSCs in vitro. The levels of M-MDSCs in newly diagnosed and relapsed MM patients were significantly increased compared with those in remission MM patients and healthy donors. Moreover, the levels of M-MDSCs were shown to correlate with tumor progression. The decrease in M-MDSCs after proteasome inhibitory therapy suggested that M-MDSCs could be considered as an indicator for the efficacy of therapy. Finally, we found the plasma from newly diagnosed MM patients, and MM cells were able to induce the accumulation of M-MDSCs in vitro. These results indicated that M-MDSCs could be considered as a prognostic predictor and an important cell type contributing to immune suppressive microenvironment in MM patients. Treatments targeting for M-MDSCs may improve therapeutic outcomes for MM patients.
authors.affiliation: Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, People's Republic of China.
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Wang
authors.forename: Lulu
authors.initials: L
authors.lastname: Zhang
authors.forename: Huiping
authors.initials: H
authors.lastname: Wang
authors.forename: Shudao
authors.initials: S
authors.lastname: Xiong
authors.forename: Yanli
authors.initials: Y
authors.lastname: Li
authors.forename: Qianshan
authors.initials: Q
authors.lastname: Tao
authors.forename: Weihua
authors.initials: W
authors.lastname: Xiao
authors.forename: Hui
authors.initials: H
authors.lastname: Qin
authors.forename: Yiping
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Zhai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002450:Cell Communication / Q000276:immunology; D048708:Cell Growth Processes / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology; D011719:Pyrazines / Q000008:administration & dosage; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D016207:Cytokines; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D011719:Pyrazines; D000069286:Bortezomib