Anti-tumor effects of endogenous prostate cancer-specific CD8 T cells in a murine TCR transgenic model

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-gamma 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. Prostate 72: 514-522, 2012. (C) 2011 Wiley Periodicals, Inc.