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

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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.
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关键词: Breast cancer B lymphocytes CD19 IL-10 PD-L1 regulatory B cell regulatory T cell

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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.

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出版当年[2015]版:
大类 | 2 区 医学
小类 | 2 区 免疫学 2 区 肿瘤学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 免疫学 2 区 肿瘤学
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出版当年[2014]版:
Q1 ONCOLOGY Q1 IMMUNOLOGY
最新[2023]版:
Q1 IMMUNOLOGY Q1 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2014版] 出版当年五年平均 出版前一年[2013版] 出版后一年[2015版]

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第一作者机构: [1]Department of General Surgery, The First Affiliated Hospital of Soochow University , Suzhou, P.R. China.
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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.
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