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Increase in CD14+HLA-DR−/low myeloid-derived suppressor cells in hepatocellular carcinoma patients and its impact on prognosis

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Abstract

Myeloid-derived suppressor cells (MDSCs) are known as key immune regulators in various human malignancies, and it is reported that CD14+HLA-DR−/low MDSCs are increased in hepatocellular carcinoma (HCC) patients. However, the host factors that regulate the frequency and the effect on the prognosis of HCC patients are still unclear. We investigated these issues and clarified the relationships between a feature of MDSCs and host factors in HCC patients. We examined the frequency of MDSCs in 123 HCC patients, 30 chronic liver disease patients without HCC, and 13 healthy controls by flow cytometric analysis. The relationships between the clinical features and the frequency of MDSCs were analyzed. In 33 patients who received curative radiofrequency ablation (RFA) therapy, we examined the impact of MDSCs on HCC recurrence. The frequency of MDSCs in HCC patients was significantly increased. It was correlated with tumor progression, but not with the degree of liver fibrosis and inflammation. In terms of serum cytokines, the concentrations of IL-10, IL-13, and vascular endothelial growth factor were significantly correlated with the frequency of MDSCs. In HCC patients who received curative RFA therapy, the frequency of MDSCs after treatment showed various changes and was inversely correlated with recurrence-free survival time. The frequency of MDSCs is correlated with tumor progression, and this frequency after RFA is inversely correlated with the prognosis of HCC patients. Patients with a high frequency of MDSCs after RFA should be closely followed and the inhibition of MDSCs may improve the prognosis of patients.

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Abbreviations

MDSCs:

Myeloid-derived suppressor cells

HCC:

Hepatocellular carcinoma

CLD:

Chronic liver disease

RFA:

Radiofrequency ablation

TACE:

Transcatheter arterial chemoembolization

PBMC:

Peripheral blood mononuclear cell

Tregs:

Regulatory T cells

HLA:

Human leukocyte antigen

FGF:

Fibroblast growth factor

CCL:

Chemokine C–C motif ligand

G-CSF:

Granulocyte colony stimulating factor

GM-CSF:

Granulocyte macrophage colony stimulating factor

IP:

Interferon gamma-induced protein

MCP:

Monocyte chemoattractant protein

MIP:

Macrophage inflammatory protein

PDGF:

Platelet-derived growth factor

RANTES:

Regulated upon activation, normal T cell expressed and secreted

TNF:

Tumor necrosis factor

VEGF:

Vascular endothelial growth factor

JAK:

Janus kinase

STAT:

Signal transducer and activator of transcription

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Acknowledgments

This study was supported by research grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, 13-1, Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan

    Fumitaka Arihara, Eishiro Mizukoshi, Masaaki Kitahara, Yoshiko Takata, Kuniaki Arai, Tatsuya Yamashita & Shuichi Kaneko

  2. Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Matsuoka, Fukui, Japan

    Yasunari Nakamoto

Authors
  1. Fumitaka Arihara
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  2. Eishiro Mizukoshi
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  3. Masaaki Kitahara
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  6. Tatsuya Yamashita
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Correspondence to Fumitaka Arihara.

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Arihara, F., Mizukoshi, E., Kitahara, M. et al. Increase in CD14+HLA-DR−/low myeloid-derived suppressor cells in hepatocellular carcinoma patients and its impact on prognosis. Cancer Immunol Immunother 62, 1421–1430 (2013). https://doi.org/10.1007/s00262-013-1447-1

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  • DOI: https://doi.org/10.1007/s00262-013-1447-1

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