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IFN-- MEDIATED UPMODULATION OF MHC CLASS I EXPRESSION ACTIVATES TUMORSPECIFIC IMMUNE RESPONSE IN A MOUSE MODEL OF PROSTATE CANCER
M. Martini1, M. G. Testi, 1 M. Pasetto1, M. C. Picchio1, G. Innamorati1, M. Mazzocco1, S. Ugel2, S.
Cingarlini3, V. Bronte2, P. Zanovello2, M. Krampera3, F. Mosna3, T. Cestari1, A.P. Riviera1, N.
Brutti1, O. Barbieri4, L. Matera5, G. Tridente1, M. Colombatti, 1 S. Sartoris1
1University of Verona, Dept. Pathology, Section Immunology, Verona, Italy, 2University of
Padova, Dept. Oncology and Surgical Sciences, Section Oncology, Padova, Italy, 3University of
Verona, Dept. Clinical and Experimental Medicine, Section Hematology, Verona, Italy.
4University of Genova, Dept. Oncology, Biology and Genetics, Genova, Italy, 5University of
Torino, Dept. Internal Medicine, Torino, Italy.
The mouse prostatic adenocarcinoma tumorigenic cell line TRAMP-C2 represents a suitable
animal model to study the role of major histocompatibility class-I (MHC-I) molecules
expression in protection against tumor development and progression in vivo. In these cell
lines, MHC-I expression decreases after time of in vitro cell culture, but it can be restored by
treatment with IFN-. We have transduced TRAMP-C2 cells with the cDNA of the costimulatory molecule B7-1. TRAMP-C2/B7 transfectants showed impaired growth in vivo, but
they did not elicit a protective response against TRAMP-C2 parental tumor, unless after
treatment with IFN- prior to injection. IFN- antagonyzes the immunosuppressant activity of
TGF-, largely produced by TRAMP-C2. Immunization with TRAMP-C2/B7 conferred
protection against TRAMP-C2-derived tumors in function of the IFN--mediated fine-tuned
modulation of either APM expression or TGF- signaling. To explore possible clinical
traslation of these results we attempted to deliver IFN- to TRAMP-C2 tumor growth site by
means of genetically engineered mesenchymal stem cells (MSCs) secreting IFN-. This
approach produced results matching those obtained with IFN--treated TRAMP-C2 cells.