Perioperative dynamic alterations in peripheral regulatory T and B cells in patients with hepatocellular carcinoma
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RESEARCH
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Perioperative dynamic alterations in peripheral regulatory T and B cells in patients with hepatocellular carcinoma Tianxiang Chen1,2, Dongli Song3, Zhihui Min3, Xiangdong Wang3, Yu Gu4, Bajin Wei1,2, Jia Yao1,2, Kangjie Chen1,2, Zhijun Jiang1,2, Haiyang Xie1,2, Lin Zhou1,2 and Shusen Zheng1,2*
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
Background Regulatory T cells (Tregs) are a subpopulation of CD4+ and CD8+ T cells with immune suppressive function. In cancer patients especially patients with hepatocellular carcinoma (HCC), Tregs contribute to the dampening of * Correspondence: [email protected] 1 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery , First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China Full list
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