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Circulating CD14+HLA-DR−/low myeloid-derived suppressor cell is an indicator of poor prognosis in patients with ESCC

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Tumor Biology

Abstract

Accumulating evidences demonstrate that a population of suppressive cells known as myeloid-derived suppressor cells (MDSCs) is key immune modulators which suppress antitumor immunity. In this study, we found that the level of circulating CD14+HLA-DR−/low cells in patients was significantly higher than that of healthy donors and was correlated with tumor burden, lymph node metastasis, and tumor, node, and metastasis (TNM) clinical stage. More importantly, we for the first time find the level of CD14+HLA-DR−/low is a biological indicator of poor prognosis through the analysis of 3-year overall survival. Furthermore, we evidenced that the proportion of CD14+HLA-DR−/low cells in the tumor metastatic tumor-draining lymph nodes (TDLNs) was notably higher compared to tumor-free TDLNs. Additionally, CD14+HLA-DR−/low cells from esophageal squamous cell carcinoma (ESCC) patients expressed dramatically increased programmed death ligand 1 (PD-L1) comparing to that from healthy control. Subsequently, blocking PD-L1 pathway by antibody could effectively reverse the suppressive effect on autologous T cell proliferation mediated by CD14+HLA-DR−/low cells in vitro. In conclusion, our data revealed CD14+HLA-DR−/low MDSCs which increase in ESCC patients is a novel poor prognostic indicator and may exert immunosuppressive properties through PD-L1/PD-1 pathway.

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Abbreviations

MDSCs:

Myeloid-derived suppressor cells

ESCC:

Esophageal squamous cell carcinoma

PD-L1:

Programmed death ligand 1

TDLNs:

Tumor-draining lymph nodes

PBMCs:

Peripheral blood mononuclear cells

ARG-1:

Arginase-1

ROS:

Reactive oxygen species

iNOS:

Inducible nitric oxide synthase

TGF-β:

Transforming growth factor β

Tregs:

Regulatory T cells

PIR-B:

Paired immunoglobulin-like receptors B

CFSE:

Carboxyfluorescein succinimidyl ester

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grants 31300746 to H.H., 81372276 to G.Z., 31320103918 to X.Z.), the Natural Science Foundation of Jiangsu (Grant BK20131158 to G.Z.), and by the Natural Science Foundation of Suzhou (Grant SYS201323 to H.H.).

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    Authors and Affiliations

    1. Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 708 Renmin Road, Suzhou, 215007, China

      Haitao Huang, Guangbo Zhang & Xueguang Zhang

    2. Jiangsu Province Key Laboratory of Stem Cell Research, Soochow University, 708 Renmin Road, Suzhou, 215007, China

      Haitao Huang, Guangbo Zhang & Xueguang Zhang

    3. Department of Cardiothoracic Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, China

      Haitao Huang, Guangbin Li & Haitao Ma

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    1. Haitao Huang
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    Correspondence to Haitao Ma or Xueguang Zhang.

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    Haitao Huang and Guangbo Zhang contributed equally to this work.

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    Huang, H., Zhang, G., Li, G. et al. Circulating CD14+HLA-DR−/low myeloid-derived suppressor cell is an indicator of poor prognosis in patients with ESCC. Tumor Biol. 36, 7987–7996 (2015). https://doi.org/10.1007/s13277-015-3426-y

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