title: Anti-tumor effects of endogenous prostate cancer-specific CD8 T cells in a murine TCR transgenic model.
abstract: BACKGROUND
  The CD8 T-cell response to prostate and other cancers is often functionally diminished or absent. This may occur via deletion of tumor-specific T cells, through acquisition of an anergic phenotype, or via active suppression mediated by another population of cells.
  
  
  METHODS
  We used a double transgenic model in which mice express CD8 T cells specific for a prostate/prostate cancer antigen to study the response of CD8 T cells to evolving autochronous prostate tumors in TRAMP mice. CD8 T cells were analyzed for functionality by measuring IFN-γ production via flow cytometry and via an in vivo CTL killing assay. In addition, pathological scoring of the prostates of the double transgenic mice was compared to scoring of tumor burden prostates of ProTRAMP mice.
  
  
  RESULTS
  Tumor-specific CD8 T cells were not grossly deleted in these animals, but evidenced a clearly non-functional phenotype. Interestingly, full lytic function was rapidly recovered upon removal from tumor-bearing mice.
  
  
  CONCLUSIONS
  These data indicate a role for continuous antigen exposure in the maintenance of tumor-specific CD8 T-cell tolerance to prostate cancer.
authors.affiliation: Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Tullia C
authors.initials: TC
authors.lastname: Bruno
authors.forename: Cristin
authors.initials: C
authors.lastname: Rothwell
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Grosso
authors.forename: Derese
authors.initials: D
authors.lastname: Getnet
authors.forename: Hung Rong
authors.initials: HR
authors.lastname: Yen
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Durham
authors.forename: George
authors.initials: G
authors.lastname: Netto
authors.forename: Drew M
authors.initials: DM
authors.lastname: Pardoll
authors.forename: Charles G
authors.initials: CG
authors.lastname: Drake
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D044584:Carcinoma, Ductal / Q000276:immunology* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000276:immunology* / Q000473:pathology; D002470:Cell Survival; D017690:Cell Transplantation; D004195:Disease Models, Animal; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019048:Prostatic Intraepithelial Neoplasia / Q000276:immunology* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology
chemical_list: D007371:Interferon-gamma