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

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

Author information

1
School of Life Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.

Abstract

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.

PMID:
21674477
DOI:
10.1002/eji.201041282
[Indexed for MEDLINE]
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