Abstract PR016: The temporal dynamics of the immune response to neoadjuvant androgen deprivation therapy suggests a window-of-opportunity for checkpoint inhibitor therapy in prostate cancer.

Abstract Purpose: Novel therapies to prevent lethal castration resistant prostate cancer in response to standard-of-care androgen deprivation therapy (ADT) are required. Unfortunately, most prostate cancers are “immune cold” and fail to respond to checkpoint inhibitors (CPIs). To assess whether ADT induces changes that enable more effective CPI therapy, we examined the tumor immune micro-environment (TiME) following neoadjuvant ADT (nADT). Design: Radical prostatectomy specimens from 43 nADT-treated patients were stratified into three duration groups and compared to each other and matched controls. RNA sequencing and quantitative multispectral immunofluorescence (qmIF) staining were performed to analyze transcriptomic and TiME abundance and cellular spatial relationship differences after nADT. Results: Immune and inflammatory pathways were increased, particularly of antigen presentation and adaptive immune response, most notably in tumors receiving 3-5 months nADT. qmIF revealed a complex temporal response in the TiME, with a dramatic influx of CTLs and T-helper cells after 3-5 months of nADT. However, after 6 months nADT, M2-like tumor associated macrophages (TAMs) and Tregs were dramatically increased while CTLs decreased. Spatially, CTLs and T-helper cells clustered near tumor cells at 3-5 months nADT but were displaced by M2-TAMs in tumors receiving ≥ 6 months of nADT. Conclusion: These data reveal the induction of a bi-phasic response in the TiME: robust CTL activation 3-5 months after nADT is initiated, followed by myeloid immunosuppression in tumors receiving prolonged nADT. This ADT-induced reprogramming of the TiME suggests a critical window of opportunity where short-duration ADT might augment CPI efficacy, converting cold into immunologically responsive tumors. Citation Format: Anmbreen Jamroze, Renyuan Zhang, Kriti Ahuja, John J. Krolewski, Dean G. Tang, Gurkamal Chatta, Kent L. Nastiuk. The temporal dynamics of the immune response to neoadjuvant androgen deprivation therapy suggests a window-of-opportunity for checkpoint inhibitor therapy in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr PR016.