title: High expression of IL-17 and IL-17RE associate with poor prognosis of hepatocellular carcinoma.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is a typical malignancy in a background of chronic inflammation. Th17 cells (a major source of IL-17) constitute crucial components of infiltrating inflammatory/immune cells in HCC and can amplify inflammatory response via binding to interleukin-17 receptor (IL-17R). Thus, we investigated the expression and clinical significance of IL-17 and IL-17 receptor family cytokines in HCC.
  
  
  METHODS
  The expression and prognostic value of IL-17 and IL-17R (A-E) were examined in 300 HCC patients after resection. Six Th17 associated cytokines in serum (n = 111) were quantified using enzyme-linked immunosorbent assays. Phenotypic features of IL-17+ CD4+ T cells were determined by flow cytometry analysis.
  
  
  RESULTS
  High expression of intratumoral IL-17 and IL1-7RE were significantly associated with poorer survival (p = 0.016 and <0.001, respectively) and increased recurrence (both P < 0.001) of HCC patients. Moreover, intratumoral IL-17, individually or synergistically with IL-17RE, could predict HCC early recurrence and late recurrence. Also, peritumoral IL-17RE showed the prognostic ability in HCC (P < 0.001 for OS/TTR). Furthermore, expression levels of Th17 associated cytokines including IL-6, -22, -17R and TNF-α were increased in serum of HCC patients compared to haemangioma patients. Importantly, activated human hepatic stellate cells induced in vitro expansion of IL-17+ CD4+ T cells.
  
  
  CONCLUSIONS
  High expression of IL-17 and IL-17RE were promising predictors for poor outcome of HCC patients. The protumor power of IL-17 producing CD4+ T cells was probably involved in the crosstalk with different types of inflammatory/immune cells in HCC.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Rd, Shanghai 200032, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liao
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Han
authors.initials: H
authors.lastname: Wu
authors.forename: Yong
authors.initials: Y
authors.lastname: Yi
authors.forename: Jia-Xing
authors.initials: JX
authors.lastname: Wang
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: He
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Cai
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Cheng
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.forename: Shuang-Jian
authors.initials: SJ
authors.lastname: Qiu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology; D005260:Female; D055166:Hepatic Stellate Cells / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D011379:Prognosis; D053722:Receptors, Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: C109985:IL17RA protein, human; D020381:Interleukin-17; D053722:Receptors, Interleukin-17