机构:[1]Department of General Surgery, The First Affiliated Hospital of Soochow University , Suzhou, P.R. China.[2]Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, P.R. China[3]Department of General Surgery, Wuxi Third People's Hospital, Wuxi, P. R. China.[3]Department Immunology, Medical College of Soochow University , Suzhou, P. R. China.[4]The Ultrasonagraphy Center of the Second Affiliated Hospital of Soochow University , Suzhou, P. R. China.[5]The Second Affiliated Hospital of Soochow University , Suzhou, P. R. China.[6]Department of Pathology, Medical College of Soochow University , Suzhou, P. R. China.[7]Jiangsu stem cell lab center , Jiangsu, Suzhou, P. R. China.[8]Department of Environmental Health, School of Public Health, Indiana University , Bloomington, IN, USA.
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.
基金:
This work was supported in part by the National Natural Science Foundation
of China grant number 81372343; social development project of Suzhou
grant number SS201246 and SYSD2012093; a project funded by the Priority
Academic Program Development of Jiangsu Higher Education Institutions
(PAPD).
第一作者机构:[1]Department of General Surgery, The First Affiliated Hospital of Soochow University , Suzhou, P.R. China.
共同第一作者:
通讯作者:
通讯机构:[6]Department of Pathology, Medical College of Soochow University , Suzhou, P. R. China.[8]Department of Environmental Health, School of Public Health, Indiana University , Bloomington, IN, USA.
推荐引用方式(GB/T 7714):
Guan Honggeng,Lan Yang,Wan Yuqiu,et al.PD-L1 mediated the differentiation of tumor-infiltrating CD19(+) B lymphocytes and T cells in Invasive breast cancer[J].ONCOIMMUNOLOGY.2016,5(2):e1075112.doi:10.1080/2162402X.2015.1075112.
APA:
Guan, Honggeng,Lan, Yang,Wan, Yuqiu,Wang, Qin,Wang, Cheng...&Xie, Fang.(2016).PD-L1 mediated the differentiation of tumor-infiltrating CD19(+) B lymphocytes and T cells in Invasive breast cancer.ONCOIMMUNOLOGY,5,(2)
MLA:
Guan, Honggeng,et al."PD-L1 mediated the differentiation of tumor-infiltrating CD19(+) B lymphocytes and T cells in Invasive breast cancer".ONCOIMMUNOLOGY 5..2(2016):e1075112