Mesenchymal stem cells induced anti-inflammatory features in B cells from breast tumor draining lymph nodes

Abstract

The immune-modulatory effect of adipose-derived stem cells (ASCs) on B cells in cancer has not been well elucidated. Herein, the interaction between B cells and ASCs isolated from the breast fat of either normal (nASCs) or breast cancer women (cASCs) was investigated. B cells derived from breast tumor draining lymph nodes were co-cultured with nASCs or cASCs and B cells proliferation was assessed in direct and transwell assays. Moreover, B cells were co-cultured with cASCs, nASCs or mesenchymal stromal cells of the tumor tissue (TSCs) and B cell cytokine production was assessed using flow cytometery. cASCs or TSCs were co-cultured with either intact or B cell depleted lymphocytes and frequencies of CD25⁺ FoxP3⁺ Tregs, IL-10⁺ or IFN-γ⁺ CD4⁺ T cells were assessed. Results showed that co-culture of B cells with ASCs in transwell chambers did not affect B cell proliferation. nASCs, however, was able to significantly reduce B cell proliferation in direct co-culture experiments (P = 0.004). The frequencies of IL-10⁺ , TNF-α⁺ , IL-2⁺ , and IFN-γ⁺ B cells were not significantly different in the co-cultures of B cells with ASCs or TSCs. But the TNF-α⁺ / IL-10⁺ B cells ratio decreased in all co-cultures, a reduction merely significant in B cell-cASCs co-culture (P = 0.01). The frequencies of CD4⁺ T cells subsets in either intact or B cell depleted lymphocytes did not undergo significant changes following co-culture with ASCs or TSCs. Therefore, ASCs is capable of inhibiting B cell proliferation in a contact dependent manner and shifting the cytokine profile of B cells toward an anti-inflammatory profile.

Keywords: B cells; IL-10; breast cancer; mesenchymal stem cells; regulatory T cells.