Open Access Research

Perioperative dynamic alterations in peripheral regulatory T and B cells in patients with hepatocellular carcinoma

Tianxiang Chen12, Dongli Song3, Zhihui Min3, Xiangdong Wang3, Yu Gu4, Bajin Wei12, Jia Yao12, Kangjie Chen12, Zhijun Jiang12, Haiyang Xie12, Lin Zhou12 and Shusen Zheng12*

Author Affiliations

1 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery ,First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

2 Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China

3 Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, China

4 Department of Surgical Oncology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

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Journal of Translational Medicine 2012, 10:14  doi:10.1186/1479-5876-10-14

Published: 25 January 2012

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.

Conclusion

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.

Keywords:
regulatory T cells; regulatory B cells; hepatocellular carcinoma; surgery; dynamic alteration; lymphocytes; clinical informatics