Abstract 1406: Analysis of immune responses as a consequence of androgen deprivation therapy in patients with biochemical progression of prostate cancer

Abstract

Abstract We evaluated the immune responses in 28 patients enrolled in a phase II trial at the National Cancer Institute (NCI). The aim was to investigate the effects of 3 months of androgen deprivation therapy (ADT) with goserelin on the immune responses in patients with biochemical progression of prostate cancer following local definitive therapy. PBMC and sera were collected before treatment and after 3 months. We performed flow cytometry to evaluate the frequencies of subsets of CD4+ and CD8+ T-cells, regulatory T-cells (CD4+ CD25hi CD127− FoxP3+), MDSCs and CD4 and CD8 recent thymic emigrants. CD4 T-cell proliferation and NK-cell lytic activity were evaluated. Serum samples were analyzed for cytokines, sCD27 and sCD40L. The baseline characteristics were: median age 64 years, testosterone 361 ng/dl, PSA 2.2 ng/ml, PSA-doubling time 7.0 months, and Gleason score 7. After 3 months of ADT we found no significant changes in NK-cell function or frequencies of NK subsets. CD4+ T-cell proliferation decreased slightly. The number of CD4+ effector memory T-cells decreased, but other CD4 subsets were unchanged. The frequencies of CD4 and CD8 recent thymic emigrants did not change. Regulatory T-cells (including the CTLA4+ subset), and the effector:Treg ratio did not change. In contrast, the frequency of granulocytic MDSC decreased (P<0.01). There was an increase in the sCD27:sCD40L ratio (P = 0.012), due to decreased sCD40L. There was a decrease in the serum levels of IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, GM-CSF and IFNγ. There were no changes in the serum levels of TNFα or CXCL2 after therapy. In conclusion, three months of ADT with goserelin did not alter the immune response in a way that would decrease the likelihood of successful immunotherapy after this treatment. The decreased MDSC and the increased sCD27:sCD40L ratio could indicate a more favorable immune environment. Citation Format: Caroline Jochems, Ravi A. Madan, Romaine I. Fernando, James L. Gulley, Kwong Y. Tsang, Jeffrey Schlom. Analysis of immune responses as a consequence of androgen deprivation therapy in patients with biochemical progression of prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1406.