Exploiting the Immunological Effects of Standard Treatments In Prostate Cancer
Final rept. 1 Mar 2007-31 Mar 2011
BRITISH COLUMBIA CANCER AGENCY VICTORIA
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We had previously demonstrated that hormone therapy HT and radiation therapy RT induce tumor-specific auto antibody responses in human prostate cancer, and this project investigated the clinical significance of these findings. In Aim 1, we showed that HT induces auto antibody and T cell responses against an antigen called PABPN1 in a mouse tumor model and that these immune responses are associated with inferior outcomes. We also showed that the combination of HTRT in this model leads to delayed tumor recurrence of a distal untreated tumor. In Aim 2, we developed methods to test prostate cancer tumor antigens for recognition by CD8 and CD4 T cells from patients, and we are now in a position to test recognition of serologically-defined tumor antigens associated with treatment-induced auto antibody responses. In Aim 3, we have almost completed assembly of prostate cancer patient cohorts with recurrent versus non-recurrent disease at 5 years posttreatment. In a collaborative project, we showed that prostate cancer vaccines frequently induce seemingly deleterious auto antibody responses in prostate cancer patients. In summary, our results indicate that the immune system has a profound influence on the efficacy of standard treatments, as well as experimental vaccines, in prostate cancer patients. With further understanding, it should be possible to steer the immune response in favor of improved clinical outcomes.
- Medicine and Medical Research