Human Prostate Cancer Immune Phenotypes After Androgen Deprivation Therapy.

5083 Background: The prostate tumor microenvironment (TME) is generally non-inflamed. However, we previously showed in pre-clinical models that androgen deprivation therapy (ADT) induces a complex immune cell infiltrate. Whether ADT similarly promotes inflammation in patients remains unclear. Therefore, we collected specimens from patients with localized prostate cancer treated with neoadjuvant degarelix and hypothesized that we could decipher key changes in the immune TME after ADT utilizing a novel cancer systems biology approach. Methods: We identified a cohort of patients treated with neoadjuvant degarelix (240mg SQ) as part of two clinical trials (NCT01696877, NCT01542021). Patients were treated with degarelix either 4 days (N = 13), 7 days (N = 17) or 14 days (N = 8) prior to radical prostatectomy. RNA was extracted from FFPE tissue and analyzed by RNAseq. To deconvolute fractional contributions of different immune cell subsets we performed CIBERSORT and Uniform Manifold Approximation and Projection (UMAP) analysis. Treatment groups were compared to a cohort of untreated matched controls (N = 37). Results: Degarelix induced a complex immune cell infiltrate in human primary prostate tumors with an increase in both pro- and anti-inflammatory cells subsets and changes in expression of immune checkpoints compared to untreated matched controls. Degarelix therapy also significant changed associated gene signatures within the lymphoid and myeloid compartments over time. Conclusions: ADT leads to profound immune remodeling within the prostate TME. Our analysis of human primary prostate tumors supports the hypothesis that the optimal time for immunologic intervention is the peri-castration period. These data also suggest that combinatorial immunotherapy strategies that target particular immune cell subsets will likely be required to successfully promote robust anti-tumor immune responses in prostate cancer.