title: Intrahepatic interleukin-17+ T cells and FoxP3+ regulatory T cells cooperate to promote development and affect the prognosis of hepatocellular carcinoma.
abstract: OBJECTIVE
  Recent studies have shown that imbalance between tumor-infiltrating interleukin (IL)-17(+) T cells and regulatory T cells (Tregs) is an important regulator of progression in various cancers, but little is known regarding this imbalance in hepatocellular carcinoma (HCC). This study explored the role of imbalance between IL-17(+) T cells and Tregs in the immunopathogenesis of HCC in patients with chronic hepatitis B (CHB) infection.
  
  
  METHODS
  Fifty-six of patient-matched tumors and peritumoral surgical specimens from 56 patient with HCC and 136 liver biopsies specimens from 46 patients with CHB, 37 with atypical hyperplasia (AH), and 53 with HCC were enrolled. The expressions of IL-17, FoxP3, CD4, and CD8 in liver tissue were measured by immunochemistry for the evaluation of liver-infiltrating lymphocytes.
  
  
  RESULTS
  The density of liver infiltrated FoxP3(+) Tregs was increased in a stepwise manner from CHB to AH then HCC, while there was a decreasing trend for the density of IL-17(+) T cells and CD8(+) T cells. In surgical specimens of less differentiated HCC, the quantity of tumor-infiltrating FoxP3(+) Tregs was significantly lower and IL-17(+) T cells and CD8(+) T cells were significantly higher. Additionally, peritumoral IL-17(+) T cells were increased in poorly differentiated HCC. High intratumoral FoxP3(+) Tregs with high intratumoral IL-17(+) T cells showed a significantly lower overall survival (OS) and disease-free survival (DFS) compared with other groups (OS, P = 0.033; DFS, P = 0.004). High intratumoral FoxP3(+) Tregs with high peritumoral IL-17(+) T cells showed a significantly lower survival rate compared with other groups (OS, P < 0.001 and DFS, P < 0.001).
  
  
  CONCLUSIONS
  Our findings suggest that intrahepatic IL-17(+) T cells and FoxP3(+) Tregs may cooperate to promote the progression of HCC.
authors.affiliation: The Third Central Clinical College of Tianjin Medical University, Tianjin, China; Department of Hepatobiliary Surgery, Institute of Hepatobiliary Disease, Tianjin, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Fengmei
authors.initials: F
authors.lastname: Wang
authors.forename: Yijun
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhengyan
authors.initials: Z
authors.lastname: Zhu
authors.forename: Yingtang
authors.initials: Y
authors.lastname: Gao
authors.forename: Zhe
authors.initials: Z
authors.lastname: Ma
authors.forename: Ruicheng
authors.initials: R
authors.lastname: Xu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Du
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology; D018450:Disease Progression; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17
keywords: IL-17+ T cells; atypical hyperplasia; chronic hepatitis B; hepatocellular carcinoma; regulatory T cells