CONICET | Buscador de Institutos y Recursos Humanos

Stimulation of murine melanoma B16 cells in vitro via TLR4 inhibits subsequent tumor growth in vivo. This could be seen in mice lacking TLR4 (TLR4lps-del), indicating that TLR4 on tumor cells but not on host antigen presenting cells is involved. We hypothesize that the activation of TLR4 on tumor cells in vitro would induce to them functional changes that could alter the maturation state of dendritic cells (DCs) present at the site of inoculation. TLR4lps-del DCs stimulated with CpG in the presence of supernantant (SN) from LPS-stimulated (SN B16+LPS) B16 cells were capable of overcoming the inhibition of activation observed when they were stimulated in the presence of non-stimulated B16-SN. The purpose of this study was to further analyze the effect of SN B16+LPS on the maturation of DC. Our results show that SN B16+LPS increases the levels of IL6, TNFα and IL12p70 produced by TLR4lps-del DCs, stimulated or not with CpG, compared to the levels produced in the presence of B16-SN (p<0.05). Tumor cell SN did not have significant levels of these cytokines. We also induced tumors with B16 cells stimulated (B16 + LPS) or not with (B16 Basal) LPS in TLR4lps-del mice. CD11c+ cells were isolated from spleen and lymph nodes. Interestingly, a higher percentage of CD11c+ cells, expressing increased levels of CD40 marker (p<0.05), were observed in group B16+ LPS compared to B16 Basal group. In contrast, animals of this group show a reduced percentage Gr1+CD11b+ cells in the spleen and lymph nodes of animals.Therefore, stimulation of murine melanoma cells with LPS promotes an improvement in the activation state of DCs in vitro and in vivo, and a diminished percentage in myeloid suppressor Gr1+CD11b+ cells.