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

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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.

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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

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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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Authors and Affiliations

  1. Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, People’s Republic of China

    Zhitao Wang, Huiping Wang, Shudao Xiong, Yanli Li, Qianshan Tao, Hui Qin & Zhimin Zhai

  2. Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China

    Lulu Zhang

  3. College of Life Science, University of Science and Technology of China, Hefei, People’s Republic of China

    Weihua Xiao

  4. Centre for Transplantation and Renal Research, Westmead Millennium Institute, The University of Sydney, Sydney, Australia

    Yiping Wang

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  1. Zhitao Wang
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Correspondence to Zhimin Zhai.

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Wang, Z., Zhang, L., Wang, H. et al. Tumor-induced CD14+HLA-DR−/low myeloid-derived suppressor cells correlate with tumor progression and outcome of therapy in multiple myeloma patients. Cancer Immunol Immunother 64, 389–399 (2015). https://doi.org/10.1007/s00262-014-1646-4

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