Regulatory B cells accumulate in tumor-draining lymph nodes and promote tumor growth (TUM9P.1015)

Abstract

Abstract Tumor metastasis to regional lymph nodes is a reliable marker for determining cancer progression and is associated with poor prognosis. However, mechanisms utilized by the tumor to modify the tumor-draining lymph node (TDLN) to facilitate metastasis remain to be identified. TDLNs from B16-F10 melanoma-bearing mice exhibit considerable B cell accumulation and lymphatic sinus growth (lymphangiogenesis) which precede and predict metastasis of solid tumors. Phenotypic characterization of B cells in mice bearing B16-F10 melanoma in the rear footpad identified preferential accumulation of T2-MZP B cells in the TDLN. Comparison of TDLNs and non-draining LNs of tumor-bearing mice with LNs and spleens from naïve mice determined that this pattern of B cell accumulation was restricted to the TDLN. B cell-deficient and immunocompetent mice reconstituted with T2-MZP B cells but not with other B cell subsets displayed accelerated tumor growth, demonstrating that T2-MZP B cells possess regulatory activity. Unlike splenic regulatory B cells, however, TDLN T2-MZP B cells did not exhibit increased IL-10 secretion, nor did they promote the conversion of naïve CD4+ T cells to CD4+Foxp3+ Tregs in the TDLN. These findings demonstrate that tumors initially signal via the lymphatic drainage to stimulate the preferential accumulation of T2-MZP regulatory B cells. This local response may be an early and critical step in generating an immunosuppressive environment to permit tumor growth and metastasis.