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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

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.

Keywords

Myeloid-derived suppressor cells Multiple myeloma Tumor progressive Bortezomib Immunosuppression 

Abbreviations

Arg-1

Arginase I

BM

Bone marrow

BMMCs

Bone marrow mononuclear cells

CD

Cluster of differentiation

CFSE

Carboxy fluorescein succinimidyl ester

CR

Complete remission

ELISA

Enzyme-linked immunosorbent assay

FACS

Fluorescence-activated cell sorter

FBS

Fetal bovine serum

G-CSF

Granulocyte colony stimulating factor

HD

Healthy donor

IC50

50 % inhibiting concentration

Ig

Immunoglobulin

iNOS

Inducible nitric oxide synthase

ISS

International staging system

MDSCs

Myeloid-derived suppressor cells

MM

Multiple myeloma

ND

Newly diagnosed

PB

Peripheral blood

PBMCs

Peripheral blood mononuclear cells

Pre-cul

Pre-culture

Rel

Relapsed

Rem

Remission

ROS

Reactive species oxygen

TGF-β

Transforming growth factor-β

Tregs

Regulatory T cells

VGPR

Very good partial remission

Notes

Acknowledgments

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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