title: Peripheral T cell tolerance occurs early during spontaneous prostate cancer development and can be rescued by dendritic cell immunization.
abstract: In the tumor-prone transgenic adenocarcinoma mouse prostate (TRAMP) mouse model we followed the fate of the immune response against the SV40 large T antigen (Tag) selectively expressed in the prostate epithelium during the endogenous transformation from normal cells to tumors. Young (5-7-week-old) male TRAMP mice, despite a dim and patchy expression of Tag overlapping foci of mouse prostate intraepithelial neoplasia, displayed a strong Tag-specific cytotoxic T lymphocyte (CTL) response after an intradermal injection of peptide-pulsed dendritic cells (DC). This response was weaker than the one found in vaccinated wild-type littermates, and was characterized by a reduced frequency and avidity of Tag-specific CTL. Early DC vaccination also subverted the profound state of peripheral tolerance typically found in TRAMP mice older than 9-10 weeks. The DC-induced CTL response indeed was still detectable in TRAMP mice of 16 weeks, and was associated with histology evidence of reduced disease progression. Our findings suggest that tumor antigens are handled as self antigens, and peripheral tolerance is associated with in situ antigen overexpression and cancer progression. Our data also support a relevant role for DC-based vaccines in controlling the induction of peripheral tolerance to tumor antigens.
authors.affiliation: Cancer Immunotherapy and Gene Therapy Program, Istituto Scientifico H San Raffaele, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Degl'Innocenti
authors.forename: Matteo
authors.initials: M
authors.lastname: Grioni
authors.forename: Andrea
authors.initials: A
authors.lastname: Boni
authors.forename: Annalisa
authors.initials: A
authors.lastname: Camporeale
authors.forename: Maria T S
authors.initials: MT
authors.lastname: Bertilaccio
authors.forename: Massimo
authors.initials: M
authors.lastname: Freschi
authors.forename: Antonella
authors.initials: A
authors.lastname: Monno
authors.forename: Cinzia
authors.initials: C
authors.lastname: Arcelloni
authors.forename: Norman M
authors.initials: NM
authors.lastname: Greenberg
authors.forename: Matteo
authors.initials: M
authors.lastname: Bellone
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000367:Age Factors; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D007108:Immune Tolerance; D007114:Immunization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011471:Prostatic Neoplasms / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000952:Antigens, Polyomavirus Transforming