title: Elevated pretherapy serum IL17 in primary hepatocellular carcinoma patients correlate to increased risk of early recurrence after curative hepatectomy.
abstract: OBJECTIVE
  Primary hepatocellular carcinoma (HCC) is usually presented in inflamed fibrotic/cirrhotic liver with extensive lymphocyte infiltration. We examined the associations between the HCC early recurrence and alterations in serum levels of inflammatory cytokines.
  
  
  METHODS
  A cohort of 105 HCC patients with chronic hepatitis B virus infection were included. Pre-therapy, we quantified their serum concentrations of Th1-, Th2-, Th17-, Treg-related, and other cytokines that have been reported to be associated with poor prognosis in human cancers. IL17-producing T-cells were generated in vitro from HCC patients and co-cultured with HCC cell lines separated by a 0.4 µM transwell.
  
  
  RESULTS
  All the 105 cases of HCC patients had liver cirrhosis. The patients who suffered from HCC early recurrence had higher pre-therapy serum levels of IL17 and lower levels of IL10 than those who did not suffer from recurrence after curative hepatectomy. After adjustment for general tumor clinicopathological factors, elevated serum levels of IL17 (≥ 0.9 pg/ml) was found to be an independent risk factor for HCC early recurrence with a hazard ratio of 2.46 (95%CI 1.34-4.51). Patients with bigger tumors (>5 cm in diameter) and elevated serum levels of IL17 had the highest risk of early recurrence as compared to those with only one of these factors (P = 0.009) or without any (P<0.001). These factors showed similar effects on the HCC patient overall survival. Intrahepatic infiltrated T-cells in HCC patients were identified as the major IL17-producing cells. Proliferation of HCC cells, QGY-7703, was augmented QGY-7703, was augmented in the presence of IL17-producing T-cells. This effect diminished after neutralizing antibody against human IL17A or TNFα was included.
  
  
  CONCLUSIONS
  Both tumors and IL17 from liver infiltrated T-cells contributed to HCC early recurrence and progression after curative resection. Pre-therapy serum IL17 levels may serve as an additional indicator for predicting high-risk patients.
authors.affiliation: Department of Surgery, Cancer Institute/Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Jianxiong
authors.initials: J
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Du
authors.forename: Liguo
authors.initials: L
authors.lastname: Liu
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Weiqi
authors.initials: W
authors.lastname: Rong
authors.forename: Liming
authors.initials: L
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Mengya
authors.initials: M
authors.lastname: Zang
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Wu
authors.forename: Yawei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Qu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000601:surgery; D002469:Cell Separation; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D006498:Hepatectomy; D006801:Humans; D020381:Interleukin-17 / Q000097:blood*; D008113:Liver Neoplasms / Q000097:blood* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D057234:Preoperative Period; D011379:Prognosis; D012307:Risk Factors
chemical_list: D020381:Interleukin-17