Coexistence of regulatory B cells and regulatory T cells in tumor-infiltrating lymphocyte aggregates is a prognostic factor in patients with breast cancer

Tumors can acquire tolerance to tumor immunity and develop enhanced proliferation. Regulatory B cells (Bregs), whose role in immune tolerance is similar to that of regulatory T cells (Tregs), appear to be involved in tumor immunity. Recently, Bregs were found to induce Tregs against tumor immunity. However, the platform for the coexistence of Bregs and Tregs in cancer patients and its clinical significance remain unclear; thus, they were evaluated in breast cancer patients. In 489 breast cancer patients, CD25- and IL10-positive Bregs and Foxp3-positive Tregs were immunohistochemically evaluated in tumor-infiltrating lymphocyte aggregates (TIL aggregates) that consisted of CD19-positive B-cell follicles and CD3-positive T-cell parafollicles. Then the correlations of the localization and existence of these cells with metastasis-free survival (MFS) were evaluated in breast cancer patients. TIL aggregates were observed in marginal regions of tumors in breast cancer patients. In the TIL aggregates, the existence of Bregs was closely related to that of Tregs (p