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, 28 (20), 3548-57

IFN-gamma-mediated Upmodulation of MHC Class I Expression Activates Tumor-Specific Immune Response in a Mouse Model of Prostate Cancer

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IFN-gamma-mediated Upmodulation of MHC Class I Expression Activates Tumor-Specific Immune Response in a Mouse Model of Prostate Cancer

Matteo Martini et al. Vaccine.

Abstract

De novo expression of B7-1 impaired tumorigenicity of TRAMP-C2 mouse prostate adenocarcinoma (TRAMP-C2/B7), but it did not elicit a protective response against TRAMP-C2 parental tumor, unless after in vitro treatment with IFN-gamma. TRAMP-C2 cells secrete TGF-beta and show low MHC-I expression. Treatment with IFN-gamma increased MHC-I expression by induction of some APM components and antagonizing the immunosuppressant activity of TGF-beta. Thus, immunization with TRAMP-C2/B7 conferred protection against TRAMP-C2-derived tumors in function of the IFN-gamma-mediated fine-tuned modulation of either APM expression or TGF-beta signaling. To explore possible clinical translation, we delivered IFN-gamma to TRAMP-C2 tumor site by means of genetically engineered MSCs secreting IFN-gamma.

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