title: Perioperative dynamic alterations in peripheral regulatory T and B cells in patients with hepatocellular carcinoma.
abstract: BACKGROUND
  Intratumoral and circulating regulatory T cells (Tregs) have been shown to be critical in the pathogenesis of hepatocellular carcinoma (HCC). However there is limited knowledge on the alterations of regulatory B cells (Bregs). We here investigated perioperative dynamic alterations of peripheral circulating Tregs and Bregs in HCC patients to reveal the relationship between regulatory lymphocytes and its clinical implications.
  
  
  METHODS
  36 patients with HCC, 6 with chronic hepatitis B infection and 10 healthy donors were enrolled for this study. Frequencies of peripheral Tregs and Bregs were measured by flow cytometry with antibodies against CD4, CD25, CD127, CD19 and IL-10 before, and after radical surgery. Then, clinical informatics of HCC patients was achieved through Digital Evaluation Score System (DESS) for the assessment of disease severity. Finally, we analysed correlations between digitalized clinical features and kinetics of circulating regulatory lymphocytes.
  
  
  RESULTS
  Level of circulating CD4+CD25+CD127- Tregs in HCC patients was significantly lower than that in healthy donors and patients with chronic hepatitis B infection before surgery, but was increased after surgery. Preoperative level of CD19+ IL-10+ Bregs in HCC patients was also significantly lower than the other groups. However it dramatically was elevated right after surgery and remained elevated compared to controls (about 7 days after surgery, P = 0.04). Frequency of circulating Tregs was correlated with circulating leukocytes, ferritin, and clinical features suggesting tumor aggressiveness including portal vein thrombosis, hepatic vein involvement and advanced clinical stages. Frequency of circulating Bregs was associated with Hepatitis B e Antigen (HBeAg) and Hepatitis B virus (HBV) DNA copy number. In addition, DESS was significantly and positively correlated with other staging systems.
  
  
  CONCLUSIONS
  Frequencies of peripheral Tregs and Bregs in HCC patients increased after surgery. These results suggest that a postoperative combination of therapies against Tregs and Bregs may be beneficial for better outcome of HCC patients after resection.
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Tianxiang
authors.initials: T
authors.lastname: Chen
authors.forename: Dongli
authors.initials: D
authors.lastname: Song
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Min
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Gu
authors.forename: Bajin
authors.initials: B
authors.lastname: Wei
authors.forename: Jia
authors.initials: J
authors.lastname: Yao
authors.forename: Kangjie
authors.initials: K
authors.lastname: Chen
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Jiang
authors.forename: Haiyang
authors.initials: H
authors.lastname: Xie
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
mesh_terms: D060151:B-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology / Q000601:surgery*; D002465:Cell Movement / Q000276:immunology; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery*; D009367:Neoplasm Staging; D019990:Perioperative Care; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*