High numbers of myeloid derived suppressor cells in peripheral blood and ascitic fluid of cirrhotic and HCC patients

Immunol Invest. 2018 Feb;47(2):169-180. doi: 10.1080/08820139.2017.1407787. Epub 2017 Nov 28.

Abstract

Background: Hepatocellular carcinoma (HCC) is the 3rd most common cause of cancer-related death worldwide. It has evolved different immune escape mechanisms, which might include emergence of lymphoid and myeloid regulatory cells. Aim of this work: To determine the numbers of Myeloid-derived suppressor cells (MDSCs) in peripheral blood and ascitic fluid in cirrhosis and HCC and their relation to IFN-γ and α-fetoprotein (α-FP).

Patients and methods: Sixty individuals were enrolled in this study; forty cirrhotic patients with ascites; twenty without HCC (Group I), and twenty with HCC (group II) as well as twenty healthy individuals as a control group (group III). The phenotype and numbers of MDSCs were analyzed in peripheral blood of all the individuals and ascitic fluid of the patients using flow cytometry. Intracellular IFN-γ and serum alfa-fetoprotein were measured.

Results: Significant increases in the relative and the mean number of peripheral blood MDSCs were found in the cirrhosis and HCC groups than in the control group, with the HCC group showing the highest number. MDSC count was negatively correlated with IFN-γ levels, while α-FP was positively correlated with MDSC% in the HCC group. MDSC count was low in ascitic fluid of both HCC and cirrhosis groups with no significant difference between the 2 groups.

Conclusion: A high frequency of MDSCs was detected in the peripheral blood of cirrhotic and HCC patients, indicating presence of immunosuppressive arms. These cells could be targeted to develop a new effective immunotherapy or an adjuvant to current therapies.

Keywords: HCC; Hepatocellular carcinoma; MDSCs; immunotherapy; myeloid-derived suppressor cells.

MeSH terms

  • Adult
  • Aged
  • Ascitic Fluid / metabolism
  • Blood Cells / pathology*
  • Blood Circulation
  • Carcinogenesis
  • Carcinoma, Hepatocellular / immunology*
  • Cells, Cultured
  • Female
  • Fibrosis / immunology*
  • Humans
  • Interferon-gamma / metabolism
  • Liver Neoplasms / immunology*
  • Male
  • Middle Aged
  • Myeloid-Derived Suppressor Cells / pathology*
  • Tumor Escape
  • alpha-Fetoproteins / metabolism

Substances

  • alpha-Fetoproteins
  • Interferon-gamma