title: PD-L1 mediated the differentiation of tumor-infiltrating CD19+B lymphocytes and T cells in Invasive breast cancer.
abstract: 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-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.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University , Suzhou, P.R. China.
authors.forename: Honggeng
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, P.R. China; Department of General Surgery, Wuxi Third People's Hospital, Wuxi, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lan
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University , Suzhou, P.R. China.
authors.forename: Yuqiu
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department Immunology, Medical College of Soochow University , Suzhou, P. R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: The Ultrasonagraphy Center of the Second Affiliated Hospital of Soochow University , Suzhou, P. R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: The Second Affiliated Hospital of Soochow University , Suzhou, P. R. China.
authors.forename: Longjiang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department Immunology, Medical College of Soochow University , Suzhou, P. R. China.
authors.forename: Yongjing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathology, Medical College of Soochow University , Suzhou, P. R. China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Liu
authors.affiliation: Jiangsu stem cell lab center , Jiangsu, Suzhou, P. R. China.
authors.forename: Xueguang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Second Affiliated Hospital of Soochow University , Suzhou, P. R. China.
authors.forename: Yecheng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology, Medical College of Soochow University , Suzhou, P. R. China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Environmental Health, School of Public Health, Indiana University , Bloomington, IN, USA.
authors.forename: Zemin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, Medical College of Soochow University , Suzhou, P. R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
keywords: B lymphocytes; Breast cancer; CD19; IL-10; PD-L1; regulatory B cell; regulatory T cell