title: Foxp3+ regulatory T cells are associated with the natural history of chronic hepatitis B and poor prognosis of hepatocellular carcinoma.
abstract: BACKGROUND
  Recent studies have focused on regulatory T cells (Tregs) in chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) and they were also conducted independently of each other.
  
  
  OBJECTIVE
  This study tried to characterize Tregs in blood and tumour infiltration, and to explore the correlations between Tregs and the context of chronic hepatitis B in HCC patients.
  
  
  METHODS
  The liver-resident Tregs and CD8(+) T cells on core biopsy were investigated using immunohistochemistry staining in individuals (n = 209) with CHB (n = 47), HCC (n = 137) or healthy controls (n = 25). Circulating Tregs were detected in the above patients with CHB (n = 27) or HCC (n = 101) by flow cytometry.
  
  
  RESULTS
  The number of tumour-infiltrating and circulating FoxP3(+) Tregs was significantly high in patients with CHB (P < 0.001). However, there were fewer intratumoural Tregs in patients with advanced HCC than those in patients with early stage HCC (P = 0.043); In contrast, the circulating Tregs frequency increased during the progression of HCC (P = 0.024). Increased tumour-infiltrating and circulating FoxP3(+) Tregs were associated with poor overall survival (P = 0.041, 0.002 respectively) and a shorter time to recurrence (P = 0.049, 0.002 respectively) in patients with early stage HCC. Tumour-infiltrating Foxp3 + Tregs were related to chronic hepatitis B natural history in HCC (P = 0.012). Neither tumour-infiltrating CD8(+) T cells nor balance of intratumoural Tregs and CD8(+) T cells correlated with prognosis of HCC.
  
  
  CONCLUSIONS
  Increased Foxp3(+) Tregs may represent a prognostic predictor in patients with early stage HCC. The CHB natural history influenced density of tumour-infiltrating Tregs in hepatocellular carcinoma patients with chronic hepatitis B viruses infection.
authors: Department of Gastroenterology and Hepatology, The Third Central Clinical College of Tianjin Medical University, Tianjin, China.
authors: Fengmei
authors: F
authors: Wang
authors: Xiang
authors: X
authors: Jing
authors: Ge
authors: G
authors: Li
authors: Tao
authors: T
authors: Wang
authors: Bin
authors: B
authors: Yang
authors: Zhengyan
authors: Z
authors: Zhu
authors: Yingtang
authors: Y
authors: Gao
authors: Qin
authors: Q
authors: Zhang
authors: Yankai
authors: Y
authors: Yang
authors: Yijun
authors: Y
authors: Wang
authors: Peng
authors: P
authors: Wang
authors: Zhi
authors: Z
authors: Du
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D016022:Case-Control Studies; D002681:China; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors