Interleukin-37 mediates the antitumor activity in hepatocellular carcinoma: role for CD57+ NK cells

Sci Rep. 2014 Jun 5;4:5177. doi: 10.1038/srep05177.

Abstract

The biological role of interleukin-37 (IL-37) in cancer is large unknown. Through immunohistochemical detection using 163 primary hepatocellular carcinoma (HCC) clinical specimens, we found the expression of IL-37 was decreased in tumor tissues, and the expression level was negatively correlated with tumor size. High expression of IL-37 in HCC tumor tissues was associated with better overall survival (OS) and disease-free survival (DFS). IL-37 expression in tumor tissues was positively associated with the density of tumor-infiltrating CD57+ natural killer (NK) cells, but not with the CD3+ and CD8+ T cells. Consistently, in vitro chemotaxis analysis showed that IL-37- overexpressing HCC cells could recruit more NK cells. The in vivo mouse model experiments also revealed that overexpression IL-37 in HCC cells significantly delayed tumor growth and recruited more NK cells into tumors tissues. Our finding suggested that IL-37 might play an important role for the prognosis of HCC patients via regulating innate immune-action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • CD57 Antigens / metabolism*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / prevention & control*
  • Cell Proliferation
  • Chemotaxis
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Interleukin-1 / metabolism*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Killer Cells, Natural / pathology
  • Liver Neoplasms / immunology
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / mortality
  • Liver Neoplasms / prevention & control*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Prognosis
  • Survival Rate
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • CD57 Antigens
  • IL37 protein, human
  • Interleukin-1