title: Regulatory T cells are associated with post-cryoablation prognosis in patients with hepatitis B virus-related hepatocellular carcinoma.
abstract: BACKGROUND
  We carried out this study to evaluate the association between regulatory T cells (Treg) and prognosis and progression after cryoablation in patients with hepatitis-B virus-related hepatocellular carcinoma.
  
  
  METHODS
  Peripheral Treg frequency in 111 patients with hepatocellular carcinoma (HCC) was detected by flow cytometry. Treg frequency and function were re-examined during patient follow up. A possible association between Treg and α-fetoprotein (AFP) was also analyzed, and the distribution of resident CD4(+) and CD8(+) T cells and FoxP3(+) T cells in the liver tissue of patients with HCC was examined by immunohistochemistry.
  
  
  RESULTS
  Treg frequency significantly increased with disease progression. Our longitudinal study showed that Treg frequency had significantly decreased in 17 patients with HCC regression following cryoablation, but the frequency had dramatically increased in 14 patients with HCC recurrence or progression. Furthermore, AFP levels varied in a way comparable with Treg frequency in patients with elevated AFP recorded before therapy. Significantly increased suppressive effects of Treg on proliferation and cytokine secretion of CD8(+) and CD4(+) T cells were observed during follow up in patients with tumor progression, but not in patients with tumor response. Moreover, the numbers of CD8(+), CD4(+), and FoxP3(+) cells infiltrating the tumors around the cryotherapeutic zones were significantly decreased after argon-helium cryoablation, and this was associated with a reduction in the FoxP3/CD8 ratio. Importantly,increased quantities of circulating CD4(+)CD25(+)FoxP3(+) Treg and tumor infiltrating FoxP3(+) cells before cryoablation were associated with high recurrence or risk of progression in HCC patients after cryoablation.
  
  
  CONCLUSIONS
  Treg variation is associated with tumor regression or progression in HCC following cryoablation and may be used as a marker to estimate HCC progression.
authors.affiliation: Center of Therapeutic Research for Hepatocellular Carcinoma, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Jun-Liang
authors.initials: JL
authors.lastname: Fu
authors.forename: Yin-Ying
authors.initials: YY
authors.lastname: Lu
authors.forename: Bao-Yun
authors.initials: BY
authors.lastname: Fu
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Wang
authors.forename: Lin-Jing
authors.initials: LJ
authors.lastname: An
authors.forename: Xin-Zhen
authors.initials: XZ
authors.lastname: Wang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zeng
authors.forename: Chun-Bao
authors.initials: CB
authors.lastname: Zhou
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Yang
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000601:surgery* / Q000821:virology; D003452:Cryosurgery / Q000379:methods*; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006509:Hepatitis B / Q000150:complications; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000601:surgery* / Q000821:virology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016896:Treatment Outcome
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