IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Two-step schedule of anti-tumor immunotherapy: anti-inflammatory treatment and dendritic cell-based vaccination
Autor/es:
P. CHIARELLA; J. BRUZZO; G. C. FERNANDEZ; M. VERMEULEN; M. VULCANO; O. D. BUSTUOABAD; R. A. RUGGIERO
Lugar:
Rio de Janeiro, Brasil
Reunión:
Congreso; 13th International Congress of Immunology; 2007
Resumen:
Although animals can be prophylactically immunized against the growth of tumor implants, most of the attempts to use immunotherapy to cause the regression of tumors once they become established have been unsuccessful. The aim of this work was to understand the nature of this refractoriness in order to elaborate an efficient immunotherapeutic schedule. By employing a strong immunogenic murine fibrosarcoma (MC-C), we have demonstrated that MC-C tumor bearing mice can generate a T-cell mediated antitumor immune response which disappears when MC-C grows over 500 mm3. This tumor-associated immunosupression was accompanied with the emergence of a systemic inflammatory condition characterized by: a) an increased number of circulating and splenic granulocytes, most of them displaying activation and high expression of Gr1+ Mac1+ markers (n=6, p<0.01); b) an increasingly circulating concentration of TNF-a , IL-1 , IL-6 cytokines and SAA and CRP phase acute proteins (n=3-5, p<0.01). Splenic Treg CD4+CD25+ were not increased. Treatment of tumor-bearing mice with anti-inflammatory drugs (synthetic corticosteroid, dexamethasone; indomethacin or a dimeric TNF-  receptor) reversed both the systemic inflammatory condition and the tumor-associated immunosupression. Although this reversion was not curative allowed an otherwise ineffective vaccination strategy -based on dendritic cells pulsed with tumor lysate- to be inhibitory on the growth of a large MC-C tumor (600 mm3), p<0.001. These results suggest that this two-step schedule using an anti-inflammatory treatment, which reverses the tumor-associated immunosupression, plus a dendritic cell-based vaccination strategy aimed to stimulate the antitumor immune response, could serve eventually as a model of immunotherapy against animal and human tumors.