Increased intratumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients

J Hepatol. 2009 May;50(5):980-9. doi: 10.1016/j.jhep.2008.12.033. Epub 2009 Mar 11.


Background/aims: To characterize IL-17-producing cells, a newly defined T helper cell subset with potent pro-inflammatory properties, in hepatocellular carcinoma (HCC) and to determine their prognostic values.

Methods: One hundred and seventy-eight HCC patients were enrolled randomly. Distribution and phenotypic features of IL-17-producing cells were determined by flow cytometry and/or immunohistochemistry.

Results: Compared with corresponding non-tumor regions, the levels of Th17 cells were significantly increased in tumors of HCC patients (P<0.001). Most intratumoral Th17 cells exhibited an effector memory phenotype with increased expression of CCR4 and CCR6. Intratumoral IL-17-producing cell density was associated with overall survival (OS, P=0.001) and disease-free survival (DFS, P=0.001) in HCC patients. Multivariate Cox analysis revealed that intratumoral IL-17-producing cell density was an independent prognostic factor for OS (HR=2.351, P=0.009) and DFS (HR=2.256, P=0.002). Moreover, the levels of intratumoral Th17 cells were positively correlated with microvessel density in tumors (r=0.616, P=0.001).

Conclusion: Accumulation of intratumoral IL-17-producing cells may promote tumor progression through fostering angiogenesis, and intratumoral IL-17-producing cell could serve as a potential prognostic marker and a novel therapeutic target for HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Count
  • Female
  • Humans
  • Interleukin-17 / metabolism*
  • Kaplan-Meier Estimate
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • Microvessels / pathology
  • Middle Aged
  • Multivariate Analysis
  • Neovascularization, Pathologic / pathology
  • Prognosis
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • T-Lymphocytes, Helper-Inducer / pathology
  • Young Adult


  • Biomarkers, Tumor
  • Interleukin-17