The Roles And Mechanism Of Regulatory B Cells In The Progression Of HBV Associated Hepatocellular Carcinoma

Background:Regulatory B cell (Breg), a recently-identified B cell subset, plays a regulatory role in protecting human from autoimmune diseases and inflammatory diseases. Breg functions primarily by secreting interleukin (IL)-10. However, the functional roles of Breg and underlying mechanisms in on the progression of hepatocellular carcinoma (HCC) still remain unknown.Design and methods:A total of 61 patients with hepatitis B virus (HBV)-related HCC (age from 28 to 71 years old,20 patients with early stage of BCLC,22 with median stage,36 with advanced stage),11 patients with HBV-associated liver cirrhosis, and 28 healthy volunteers were enrolled in the study. Through flow cytometry and immunohistochemical staining, the percentage of Breg in peripheral blood and liver tissues were analyzed. In 34 patients with early and median stage who underwent resection operation, the disease-free survival (DFS) was calculated by using Kaplan-Meier method according to the median Breg count. In 27 inoperable patients with advanced stage, the overall survival time (OS) was calculated by using Kaplan-Meier method according to the median Breg count.Results:The Breg frequency in peripheral blood of HCC patients was significantly increased as compared with healthy volunteers. Furthermore, Breg in HCC liver tissues was mainly enriched in the junction site of cancer, followed by site adjacent to cancer and intralesional site. Survival analysis showed that Breg frequency in peripheral blood and livers of HCC patients was positively correlated with tumor recurrence time, and was an independent predictor of survival and tumor recurrence in these HCC patients.Conclusion:The increased Breg cells are closely associated with the progression of HCC. This study suggests that the Breg cells could be used as an immunological marker to predict the survival time and tumor recurrence in HCC patients.