Autor: |
Guan, Honggeng, Lan, Yang, Wan, Yuqiu, Wang, Qin, Wang, Cheng, Xu, Longjiang, Chen, Yongjing, Liu, Wenting, Zhang, Xueguang, Li, Yecheng, Gu, Yongping, Wang, Zemin, Xie, Fang |
Zdroj: |
OncoImmunology; February 2016, Vol. 5 Issue: 2 |
Abstrakt: |
ABSTRACTAccumulating 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-L1hiMDA-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. |
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