Dynamic analysis of tumor-associated immune cells in DEN-induced rat hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is an aggressive disease with poor prognosis and limited methods to predict patient survival. Immune cells infiltrating tumors are known to impact tumor progression. Here, we analyzed the phenotype and function of dendritic cells (DCs), and the frequency of IL-10-producing regulatory B cells (Breg) and Foxp3(+) regulatory T cells (Treg) in different stages of N-nitrosodiethylamine (DEN)-induced rat HCC in order to understand their roles in this disease. 4 weeks following DEN treatment, no significant differences in CD80 and CD86 expression were found on DCs from HCC rats and normal rats but 12 and 16 weeks following DEN treatment, the expression of CD80, CD86 and MHCII on DCs of HCC rats was significantly decreased. We also found that the frequency of IL-10-producing Breg and CD4(+)CD25(+)Foxp3(+) Treg in HCC rats was obviously increased during all of these three stages. In addition, the bone-marrow derived DCs (BMDCs) from HCC rats displayed lower ability in activating T cells and an increase in IL-10 secretion. No differences in IL-12 level and endocytosis ability were found on BMDCs from HCC rats and normal rats. Our results suggest that the dysfunction of DCs and the increase of IL-10-producing Breg and Foxp3(+) Treg might play important roles in HCC progression. (C) 2014 Elsevier B.V. All rights reserved.