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Cancer Immunology, Immunotherapy

, Volume 62, Issue 8, pp 1421–1430 | Cite as

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

  • Fumitaka Arihara
  • Eishiro Mizukoshi
  • Masaaki Kitahara
  • Yoshiko Takata
  • Kuniaki Arai
  • Tatsuya Yamashita
  • Yasunari Nakamoto
  • Shuichi Kaneko
Original Article

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.

Keywords

Myeloid-derived suppressor cells Hepatocellular carcinoma Radiofrequency ablation Recurrence Cancer 

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

Notes

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.

Supplementary material

262_2013_1447_MOESM1_ESM.pdf (786 kb)
Supplementary material 1 (PDF 785 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Fumitaka Arihara
    • 1
  • Eishiro Mizukoshi
    • 1
  • Masaaki Kitahara
    • 1
  • Yoshiko Takata
    • 1
  • Kuniaki Arai
    • 1
  • Tatsuya Yamashita
    • 1
  • Yasunari Nakamoto
    • 2
  • Shuichi Kaneko
    • 1
  1. 1.Department of Gastroenterology, Graduate School of MedicineKanazawa UniversityKanazawaJapan
  2. 2.Second Department of Internal Medicine, Faculty of Medical SciencesUniversity of FukuiMatsuokaJapan

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