Regulatory B cells, a new role for B cells in cáncer (PART II)

MAGLIOCO ANDREA; MACHUCA DAMIAN; MARIA NOEL BADANO; CAMICIA GABRIELA; CAMERANO GABRIELA; COSTA HÉCTOR; RUGGIERO RAÚL; GIORDANO MIRTA; DRAN GRACIELA

Congreso; LXI Reunión Anual de la Sociedad Argentina de Inmunología (SAI); 2013

B cells have usually been considered as antigen presenting and antibody secreting cells. However, in the last few years, a new role as regulatory cells has been described mainly in the context of autoimmune disease, while it is still controversial in cancer. In a previous work using the murine fibrosarcoma MCC we detected that tumor growth induced an increase in total and IL-10 expressing B cells within the lymph nodes. B cells from tumor bearing mice (TBM) were able to inhibit allogeneic proliferation, partially through the release of IL-10. The aim of this work was to get further into the role of B cells in the MCC model. We depleted B cells by administering anti-CD20 (10 mg/kg) to TBM on day 10 post tumor inoculation. We observed a significant inhibition of tumor growth since day 5 after antibody administration compared to mice inoculated with an irrelevant IgG as control (40 animals per group, p < 0.001). Moreover, we found an increase in the cytotoxic activity of CD3+ cells isolated from B cell depleted mice tumors (JAM Test, n = 4, p < 0.001). Additionally, using FACS we found that B cell depletion induced a decrease in the number of regulatory (CD4+Foxp3+) T cells (n = 4, p < 0.05 ), an increase in the number of activated (CD25+ IFNɣ+) CD8 + T cells (n = 4, p < 0.01) and a higher expression of CD40 on dendritic cells (n = 4, p< 0.05) in TBM lymph nodes. Our results indicate that B cells, secreting IL-10 affect MCC tumor growth by inhibiting the antitumor immune response and contributing to the tolerance state detected in advanced tumors bearing mice