Abstract
Regulatory T cells (Tregs), a key mediator in regulating anti-tumor immune suppression, tumor immune escape, metastasis and relapse, are considered an important therapeutic target in immunotherapy of human cancers. In the present investigation, elevated CD19+ CD24+ CD38+ regulatory B cells (Bregs) were observed in PBMCs of invasive carcinoma of breast (IBCa) patients compared with that in patients with fibroadenoma (FIBma) or healthy individuals, and the positive correlation existed between Bregs and CD4+ CD25+ CD127− Tregs (r = 0.316, P = 0.001). We found that PD-L1 expression was higher on Bregs in IBCa patients compared with patients with FIBma or healthy individuals (P < 0.05, respectively), and that a tight correlation exists between CD19+ CD24+ CD38+ PD-L1+ Bregs and CD19+ CD24+ CD38+ Bregs (r = 0.267, P = 0.007), poor TNM phases and up-regulated expression of PD-L1 on Bregs. The pattern of PD-1 expression on CD4+ T cells indicated that high level of PD-1hi expressed on CD4+ CD25+ CD127+ effector T cells (P < 0.001). More importantly, the presence of PD-L1 on Bregs was positively correlated with Tregs (r = 0.299, P = 0.003), but negatively correlated with PD-1hi effector T cells (r = −0.22, P = 0.031). Together, results of the present study indicated that PD-L1 is an important molecule on Bregs, mediated the generation of Tregs in IBCa.
Highlights
Regulatory B cells (Bregs), a subset of B cells, play a suppressive role in autoimmune diseases, inflammation, and anti-tumor immune response[1,2,3,4,5]
We evaluated the percentages of CD4+ T cells and its subsets in the peripheral blood mononuclear cells (PBMCs) of breast tumor patients
Because programmed death-1 (PD-1) is an important molecule in immune suppression, we evaluated the expression of PD-1 on CD4+ T cells and its subsets including CD4+CD25+CD127low/− Tregs in PBMCs
Summary
Regulatory B cells (Bregs), a subset of B cells, play a suppressive role in autoimmune diseases, inflammation, and anti-tumor immune response[1,2,3,4,5]. Programmed death-ligand 1 (PD-L1), as a critical suppressive molecule, constitutively expresses on B lymphocytes, T lymphocytes, dendritic cells and monocytes[15,16,17]. It is clear that there was an increased number of CD19+ CD24+ CD38+ Bregs in the peripheral blood mononuclear cells (PBMCs) of IBCa patients[12], it is not currently known whether PD-1/PD-L1 expressed on CD19+ CD24+ CD38+ Bregs acts exclusively on Tregs or other components of IBCa. In the present study, in an effort to further understand the role of Bregs in the etiology and pathogenesis of breast cancer, we examined CD4+ T cells, CD19+ B cells and their subsets in PBMCs of breast tumor patients, and investigated the relationship among CD4+ T cells, CD19+ B cells and their subsets in breast tumor
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