IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Unveiling antigens in a non-immunogenic spontaneous murine tumor using dendritic cell-based vaccine
Autor/es:
PAULA CHIARELLA; VERONICA REFFO; JUAN BRUZZO; RUGGIERO RAUL
Reunión:
Congreso; LVIII Reunion Anual de la Sociedad Argentina de Inmunologia; 2010
Resumen:
Most attempts to use immunotherapy to cause the regression of animal and human established tumors have not been effective. Former experiments have suggested that this failure could be related to a lack of immunogenicity of spontaneous tumors. We have investigated if this lack of immunogenicity can be attributed to the absence of tumor antigens or to the existences of tolerogenic mechanisms preventing such antigens from initiating an antitumor immune response. We use two different tumors-a non-immunogenic spontaneous lymphoma (LB) and an immunogenic fibrosarcoma (MCC)-, and, dendritic cells (DC) loaded with tumor lysate as immunization assays. When DC were pulsed with LB lysate (DC+LB), no maturation of DC was achieved and no protection against LB after DC+LB inoculation was observed. We also demonstrated that DC pulsed with MCC lysate (DC+MCC) induce the maturation of DC, producing a strong protection against MCC implants after DC+MCC inoculation. When DC were pulsed with both lysates (DC+MCC+LB), we observed a mild maturation of DC, a significant protection against LB (p<0.001) and a reduction of the protection against MCC (p<0.01). As LB and MCC have not common antigens, we suggest that: LB bears specific tumor antigens but lacks other signals to achieve DC maturation that are provided by MCC lysate. In addiction, LB would display active tolerogenic mechanisms which reduce the protection against MCC when DC+MCC+LB (p<0.001) are inoculated in vivo. These tolerogenic mechanisms seem to be associated with the high expression of pSTAT3 in LB cells, since inhibition of pSTAT3 by treating LB bearing mice with the specific inhibitor JSI-124, reduced LB tumor growth associated with the emergence of a specific anti-tumor immune response. We propose that the high expression of pSTAT3 is one of the reasons by which the LB tumor behaves as a non-immunogenic, and that targeting its expression might promote an efficient antitumor immune response against this spontaneous tumor.