The significance of cytokine-producing B cells in breast tumor-draining lymph nodes

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. 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. 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. 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.