Cancer Immunology, Immunotherapy

, Volume 64, Issue 3, pp 389–399 | Cite as

Tumor-induced CD14+HLA-DR−/low myeloid-derived suppressor cells correlate with tumor progression and outcome of therapy in multiple myeloma patients

  • Zhitao Wang
  • Lulu Zhang
  • Huiping Wang
  • Shudao Xiong
  • Yanli Li
  • Qianshan Tao
  • Weihua Xiao
  • Hui Qin
  • Yiping Wang
  • Zhimin ZhaiEmail author
Original Article


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.


Myeloid-derived suppressor cells Multiple myeloma Tumor progressive Bortezomib Immunosuppression 



Arginase I


Bone marrow


Bone marrow mononuclear cells


Cluster of differentiation


Carboxy fluorescein succinimidyl ester


Complete remission


Enzyme-linked immunosorbent assay


Fluorescence-activated cell sorter


Fetal bovine serum


Granulocyte colony stimulating factor


Healthy donor


50 % inhibiting concentration




Inducible nitric oxide synthase


International staging system


Myeloid-derived suppressor cells


Multiple myeloma


Newly diagnosed


Peripheral blood


Peripheral blood mononuclear cells








Reactive species oxygen


Transforming growth factor-β


Regulatory T cells


Very good partial remission



This work was supported by Natural Science Foundation of China (81272259, 81401293) and Natural Science Foundation of Anhui Province (KJ2014Z017, KJ2013Z121). We are grateful to the volunteers who participated in this study.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Zhitao Wang
    • 1
  • Lulu Zhang
    • 2
  • Huiping Wang
    • 1
  • Shudao Xiong
    • 1
  • Yanli Li
    • 1
  • Qianshan Tao
    • 1
  • Weihua Xiao
    • 3
  • Hui Qin
    • 1
  • Yiping Wang
    • 4
  • Zhimin Zhai
    • 1
    Email author
  1. 1.Department of HematologyThe Second Affiliated Hospital of Anhui Medical UniversityHefeiPeople’s Republic of China
  2. 2.Department of HematologyThe First Affiliated Hospital of Anhui Medical UniversityHefeiPeople’s Republic of China
  3. 3.College of Life ScienceUniversity of Science and Technology of ChinaHefeiPeople’s Republic of China
  4. 4.Centre for Transplantation and Renal Research, Westmead Millennium InstituteThe University of SydneySydneyAustralia

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