IFN-γ-mediated upmodulation of MHC class I expression activates tumor-specific immune response in a mouse model of prostate cancer

Matteo Martini, Maria Grazia Testi, Matteo Pasetto, Maria Cristina Picchio, Giulio Innamorati, Marta Mazzocco, Stefano Ugel, Sara Cingarlini, Vincenzo Bronte, Paola Zanovello, Mauro Krampera, Federico Mosna, Tiziana Cestari, Anna Pia Riviera, Nadia Brutti, Ottavia Barbieri, Lina Matera, Giuseppe Tridente, Marco Colombatti, Silvia Sartoris

Research output: Contribution to journalArticlepeer-review

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-γ. TRAMP-C2 cells secrete TGF-β and show low MHC-I expression. Treatment with IFN-γ increased MHC-I expression by induction of some APM components and antagonizing the immunosuppressant activity of TGF-β. Thus, immunization with TRAMP-C2/B7 conferred protection against TRAMP-C2-derived tumors in function of the IFN-γ-mediated fine-tuned modulation of either APM expression or TGF-β signaling. To explore possible clinical translation, we delivered IFN-γ to TRAMP-C2 tumor site by means of genetically engineered MSCs secreting IFN-γ.

Original languageEnglish
Pages (from-to)3548-3557
Number of pages10
JournalVaccine
Volume28
Issue number20
DOIs
Publication statusPublished - Apr 30 2010

Keywords

  • IFN-γ
  • MHC-I
  • TRAMP

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

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