CD21 lo/med CD27 + proinflammatory B cells are enriched in breast cancer patients and promote antitumor T cell responses.

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 CD21 ^lo/med CD27 ⁺ 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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