Modulation of T Cell Tolerance in a Murine Model for Immunotherapy of Prostatic Adenocarcinoma. Addendum
Abstract
The goal of this project is to characterize T cell tolerance to prostate tumor antigens and to identify the role of costimulatory receptors in overcoming this tolerance. Identification of these processes will assist in the development of novel therapeutic approaches for treating prostate cancer. We use the TRAMP model a transgenic mouse line that develops primary prostatic tumors due to expression of the SV40 T antigen (TAg) under the transcriptional control of a prostate-specific promoter. In this final addendum summary we report that subsequent to adoptive transfer of naive TAg-specific T cells into TRAMP mice there is rapid expansion and contraction of the tumor-specific T cells followed by accumulation of a population of T cells that persist in the prostate as tolerant and suppressive. Co-transfer of TAg-specific CD4+ T cells delays the tolerant suppressive phenotype of prostate-tumor-specific T cells. Transfer of CD4+ T cells does not reverse tolerance of previously-tolerized CD8+ cells. The suppressive nature of these CD8+ T cells was also studied and we demonstrate that suppression is at least in-part mediated by secreted factors. Further we demonstrate that trafficking od T cells to the TRAMP prostate may be mediated by chemokines. These data demonstrate the critical balance between T cell activation and tolerance and support a mechanism by which tumor growth may induce tolerance and suppressor activity in T cells previously primed to tumor-specific antigens. A greater understanding of how tolerance of these tumor specific T cells can be reversed will certainly lead to more potent anti-tumor immunotherapies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2007
- Accession Number
- ADA476016
Entities
People
- Arthur A. Hurwitz
Organizations
- State University of New York