Characterization of B cell-mediated PD-1/PD-L1 interaction in pancreatic cancer patients.

Pancreatic ductal adenocarcinoma (PDAC) is a common type of pancreatic cancer with one of the worst survival rate of all malignancies. Recent studies have identified that immunosuppressive B cells could employ the PD-1/PD-L1 pathway to suppress antitumor T cell responses, hence, we examined the expression and function of PD-L1 in B cells. We found that the PD-L1 expression was significantly enriched in tumor-infiltrating (TI) B cells than in peripheral blood (PB) B cells from the same patients. Additionally, the PB B cells from stage III and stage IV PDAC patients presented significantly higher PD-L1 than the PB B cells from healthy controls. High PD-L1 expression in PB B cells could be achieved by stimulation via CpG and less effectively via anti-BCR plus CD40L, but not by coculture with pancreatic cancer cell lines in vitro. Also, STAT1 and STAT3 inhibition significantly suppressed PD-L1 upregulation in stimulated B cells. CpG-stimulated PB B cells could inhibit the IFN-gamma expression and proliferation of CD8 T cells in a PD-L1-dependent manner. Also, TI CD8 T cells incubated with whole TI B cells presented significantly lower IFN-gamma expression and lower proliferation, than TI CD8 T cells incubated with PD-L1(+) cell-depleted TI B cells, suggesting that PD-L1(+) B cells could also suppress CD8 T cells in the tumor. Overall, this study identified that B cells could suppress CD8 T cells via PD-L1 expression, indicating a novel pathway of immuno-regulation in pancreatic cancer.