Radiation-Induced Immune Modulation in Prostate Cancer
Annual rept. 1 Jan-31 Dec 2006
CALIFORNIA UNIV LOS ANGELES
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This effort is to determine if radiation affects presentation of prostate specific antigen PSA through endogenous and exogenous pathways by dendritic cells DCs and to devise novel strategies to translate radiation-induced cell death into the generation of tumor-specific immunity. The goal is to improve the therapeutic outcome from radiation therapy. Radiotherapy is normally thought of as being immune suppressive because it kills radiosensitive lymphocytes. Our hypothesis, in contrast, is that it also affects immune cell function and this has profound effects on the immune system and the development of anti-tumor immunity. We chose PSA as antigen for this study. However, because of the high risk nature of the experiments and the high PSA expression levels in prostate cancer patients that might interfere with its efficacy, we have also develop a back-up system using survivin as an antigen, since it also is overexpressed in prostate cancer. One aim of this proposal is to devise strategies to avoid radiation-induced immunosuppression and to translate radiation tumor cytotoxicity into beneficial tumor immunity with combination treatments of IL-3 andor GM-CSF. Our studies on combined treatments of radiotherapy and IL-3, and on the effects of radiation on PSA presentation by DCs are presented, along with other milestones that have been attained.
- Medicine and Medical Research