Interleukin-17-educated monocytes suppress cytotoxic T-cell function through B7-H1 in hepatocellular carcinoma patients

Eur J Immunol. 2011 Aug;41(8):2314-22. doi: 10.1002/eji.201041282. Epub 2011 Jul 4.


Substantial evidence indicates that inflammation is a critical component of tumor progression. The proinflammatory IL-17-producing cells have recently been detected in tumors, but the effect of IL-17 on antigen-presenting cells in tumors is presently unknown. We recently found that B7-H1(+) macrophages (Mφs) were enriched predominantly in the peritumoral stroma of hepatocellular carcinomas (HCCs). Here, we found a positive correlation between IL-17-producing cells and B7-H1-expressing Mφs in the same area. The B7-H1(+) monocytes/Mφs from HCC tissues expressed significantly more HLA-DR, CD80, and CD86 than B7-H1(-) cells. Accordingly, IL-17 could activate monocytes to express B7-H1 in a dose-dependent manner. Although culture supernatants derived from hepatoma cells also induced B7-H1 expression on monocytes, IL-17 additionally increased hepatoma-mediated B7-H1 expression. Autocrine inflammatory cytokines released from IL-17-activated monocytes stimulated B7-H1 expression. Moreover, these IL-17-exposed monocytes effectively suppressed cytotoxic T-cell immunity in vitro; the effect could be reversed by blocking B7-H1 on those monocytes. Consistent with this, cytotoxic T cells from HCC tissues expressed significant B7-H1 receptor programmed death 1 (PD-1) and exhibited an exhausted phenotype. These data reveal a fine-tuned collaborative action between different stromal cells to counteract T-cell responses in tumors. Such IL-17-mediated immune tolerance should be considered for the rational design of effective immune-based anti-cancer therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • Apoptosis Regulatory Proteins / immunology
  • Apoptosis Regulatory Proteins / metabolism
  • B7-H1 Antigen
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Count
  • Cells, Cultured
  • Coculture Techniques
  • Cytotoxicity, Immunologic / drug effects
  • Cytotoxicity, Immunologic / immunology
  • Female
  • Flow Cytometry
  • Hep G2 Cells
  • Humans
  • Immunohistochemistry
  • Interleukin-17 / immunology*
  • Interleukin-17 / metabolism
  • Interleukin-17 / pharmacology
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Programmed Cell Death 1 Receptor
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • Th17 Cells / immunology
  • Th17 Cells / metabolism
  • Young Adult


  • Antigens, CD
  • Apoptosis Regulatory Proteins
  • B7-H1 Antigen
  • CD274 protein, human
  • Interleukin-17
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor