CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
ACTIVATION OF TLR4 ON TUMOR CELLS IN VITRO INHIBITS FURTHER TUMOR GROWTH IN VIVO.
Autor/es:
V. ANDREANI, G. GATTI, L. SIMONELLA, V. RIVERO, M. MACCIONI.
Lugar:
Rio de Janeiro, Brasil
Reunión:
Congreso; 13th International Congress of Immunology; 2007
Institución organizadora:
IUIS
Resumen:
Whereas an eruption of information regarding the role of Toll like receptor 4 (TLR4), the main receptor for bacterial lipopolysaccharide, in activating macrophages and dendritic cells has emerged, very little is known about the role of TLR4 present on epithelial cells from sterile environments, like tumors. The main goal of this work was to investigate the consequences of TLR4 activation present on tumor cells in two different animal models of cancer: the Dunning rat prostate cancer and the B16 murine melanoma models. We demonstrate that a) activating TLR4 signaling in two different tumor cell lines in vitro modifies the tumor outgrowth in vivo; b) this effect is not due to a direct consequence of TLR4 signaling on the proliferation/apoptosis balance of the tumor cells; c) the T cell compartment is somehow involved in the described phenomenon since the inhibitory effect observed is not seen in athymic nude mice; d) and that tumor infiltrating lymphocytes purified from tumors induced by TLR4-activated cells show strong induction of INF ã transcript in detriment of IL10 transcript, suggesting a change in their functionality. We hypothesize that TLR4 signaling in tumor cells in vitro induces the expression of proinflammatory mediators, which could dramatically alter the maturation state of dendritic cells present at the site of inoculation, switching the type of immune response elicited against the tumor. These results open up new avenues for understanding the role of TLR4 on tumor cells and for identifying potential new therapy strategies for cancer.