CD21lo/medCD27+ proinflammatory B cells are enriched in breast cancer patients and promote antitumor T cell responses

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Abstract

Breast cancer is a common malignancy and a major cause of death in women worldwide. The immunomodulatory role of B cells is being increasingly recognized in autoimmune diseases and cancers. In recent years, immunotherapeutic strategies that upregulate the patient's own antitumor T cell responses have shown promise in treating solid tumors and are being developed for breast cancer. In this study, we discovered that the B cells in breast cancer patients were enriched with interferon (IFN)-γ-expressing cells and presented high potency for IFN-γ production. These IFN-γ-expressing B cells were enriched in, but did not completely overlap with, the CD21lo/medCD27+IgM-IgD-IgG+IgA- B cell subset, which was consistent with IgG-expressing memory B cells. Compared to CD27+IgG- B cells, the CD27+IgG+ B cells expressed significantly higher IFN-γ expression. Given that B cells demonstrate important antigen-presenting function to T cells, we incubated CD27+IgG- B cells and CD27+IgG+ B cells with autologous CD4+ T cells. Compared to the CD4+ T cells that were incubated with CD27+IgG- B cells, the CD4+ T cells that were incubated with CD27+IgG+ B cells presented significantly higher TBX21 and lower FOXP3 expression, suggesting that the CD27+IgG+ B cells, but not the CD27+IgG- B cells, promoted Th1 and suppressed regulatory T cell responses. IFN-γ-expressing B cells were further enriched in the intratumoral environment of breast cancer patients. Together, we discovered that breast cancer patients presented an upregulation of IFN-γ-expressing proinflammatory B cells with the potency to promote Th1 responses.

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