Abstract: Radiation therapy (RT) is the front line treatment for prostate cancer in the early stages but is relatively ineffective against large tumor volumes and it is difficult to use it against micrometastatic disease. Immunotherapy (IT) has become popular as an alternative treatment since the discovery of prostate tumor-associated antigens (TAA) and of corresponding tumor-specific T cells in prostate cancer patients. However, IT is not a very effective modality on its own due to multiple tumor escape mechanisms and probably would benefit from combination with other therapies, such as RT. At least in theory, a potential advantage is that radiation affects the immune system by upregulating MHC class I and co-stimulatory molecules, which could promote T cell filtration into tumors and T cell activation. On the other hand, we recently showed that radiation affects proteasome function, which could affect antigen processing, and appears to have other effects on DC antigen presentation. In the first year of this study, we have been constructing cell lines to examine this in prostate cancer. We have also examined the effects of radiation on DC processing PSA either endogenously or exogenously as well as on proteasome and immunoproteasome function in DCs. The final goal of the proposal is to determine if radiation affects the hierarchy of antigenic peptide presented by DCs and tumor cells and to devise better strategies in combination treatments of RT and IT.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Annual rept. 1 Feb 2007-31 Jan 2008 |
| Pages: |
42 |
| Report Date: |
FEB 2008 |
| Contract Number: |
W81XWH0710135 |
| Report Number: |
A859284 |
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