title: Interleukin-17-educated monocytes suppress cytotoxic T-cell function through B7-H1 in hepatocellular carcinoma patients.
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.
authors.affiliation: School of Life Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Qiyi
authors.initials: Q
authors.lastname: Zhao
authors.forename: Xiao
authors.initials: X
authors.lastname: Xiao
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wei
authors.forename: Ling-Yan
authors.initials: LY
authors.lastname: Zhu
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
authors.forename: Dong-Ming
authors.initials: DM
authors.lastname: Kuang
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000276:immunology / Q000378:metabolism; D060890:B7-H1 Antigen; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D002478:Cells, Cultured; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008113:Liver Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D020381:Interleukin-17; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor