Abstract
PURPOSE: The role of cytokine-producing B cells in antitumor immunity is mostly overlooked. In the present study, we investigated changes in B cell cytokine profiles in breast tumor-draining lymph nodes (TDLNs) during disease progression, and associations of these changes with prognostic indicators. METHODS: Flow cytometry was used to measure the expression of TNF-α, IL-10, TGF-β, IL-2 and IFN-γ in B cells from 42 axillary lymph nodes. The frequencies of IL-10(+) and FoxP3(+) T regulatory cells (Tregs) were also determined. RESULTS: No significant changes in B cell cytokine profiles were observed during breast cancer progression from stage I to III, but the percentage of B cells with high TNF-α expression (TNF(hi)) showed a negative relationship with lymph node involvement and Her2 expression (p < 0.05). The percentage of IL-10(+) B cells was found to be significantly higher in non-metastatic lymph nodes in node-negative compared to node-positive patients (p = 0.001). The frequencies of IL-10(+) and TNF(hi) B cells were found to be negatively correlated with the number of involved lymph nodes. The frequency of TNF(hi) B cells showed an inverse correlation with the frequency of FoxP3(+) Tregs, which in turn was associated with indicators of a poor prognosis. CONCLUSIONS: Our data indicate that the cytokine profiles of B cells in TDLNs of patients with breast cancer show associations with various disease parameters. TNF(hi) and IL-10(+) B cells correlated positively with indicators of a good prognosis. Further functional studies are required to elucidate the role of cytokine production by B cells in immunity against breast cancer.