PD-L1 mediated the differentiation of tumor-infiltrating CD19(+) B lymphocytes and T cells in Invasive breast cancer

摘要

Accumulating evidence suggests that B cells play important roles in inhibiting the immune response in autoimmune disorders and human tumors as well as murine tumor models. In an effort to explore the role of B cells in human breast cancer etiology, we examined the presence of CD19(+) B lymphocytes in 134 cases of invasive breast carcinoma (IBCa) and 31 breast fibroadenoma, and assessed its relationship with PD-L1 (programmed death-ligand 1) expression in breast cancer. We found that the density of CD19(+) B lymphocytes was higher in IBCa compared with fibroadenoma, and significantly associated with increasing tumor grade, negative estrogen status. Similar findings were observed for the expression of IL-10 in IBCa. Meanwhile, CD19(+) B lymphocytes were shown to be highly coincident with PD-L1 and IL-10 in IBCa. We further demonstrated that CD19(+) B cells can differentiate into CD19(+)CD24(+)CD38(+) B cells when co-cultured with PD-L1(hi) MDA-MB231 cells. In addition, the percentage of CD19(+)CD24(+)CD38(+) B cells was higher in breast tissue and peripheral blood cells of IBCa patients than that of benign tumor and health individuals. And CD19(+)CD24(+)CD38(+) B cells were found to be IL-10 secreting B cells. Finally, we showed that CD19(+) B cells from IBCa patients but not healthy individuals induced formation of CD4(+)CD25(+)Foxp3(+) T cells when co-cultured with T cells from IBCa patients and healthy subjects (80.4% and 30.8% respectively). The induction of CD4(+)CD25(+)Foxp3(+) T cells by CD19(+) B cells was further shown to be mediated by PD-L1. Together, these results are suggestive of a role for CD19(+) B lymphocytes in immune suppression and tumor evasion via PD-L1 in breast cancer.