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

Vaccine. 2010 Apr 30;28(20):3548-57. doi: 10.1016/j.vaccine.2010.03.007. Epub 2010 Mar 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / immunology*
  • Animals
  • B7-1 Antigen / genetics
  • B7-1 Antigen / immunology
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Genes, MHC Class I
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology*
  • Interferon-gamma / immunology*
  • Male
  • Mesenchymal Stem Cells / immunology
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / immunology
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / immunology*
  • Spleen / cytology
  • Spleen / immunology
  • Transfection
  • Transforming Growth Factor beta / immunology
  • Up-Regulation


  • B7-1 Antigen
  • Histocompatibility Antigens Class I
  • Transforming Growth Factor beta
  • Interferon-gamma