Abstract A023: Differential Patterns of Immune Infiltration in the Tumor Immune Microenvironment Associate with Therapeutic Response in Primary Prostate Cancer Following Chemohormonal Therapy

Abstract Background: There is a critical need to develop novel therapeutic strategies and diagnostic tools to precisely deliver treatments to improve survival for men with prostate cancer (PCa). To support this development, improved strategies are needed to better understand heterogenous tumor microenvironments and tumor biology that associate with variable treatment responses. We hypothesized that the tumor immune microenvironment (TIME) plays a critical role in treatment resistance. In this study we aimed to evaluate TIME signatures of treatment response and resistance utilizing a novel, integrated technological tool to identify response patterns and enable precision sampling for comparative cellular and molecular analysis. Methods: 30 patients with newly-diagnosed, locally advanced, high-risk, primary PCa underwent 18F-DCFPyL PSMA PET with multiparametric MRI (mpMRI) imaging on a dedicated PET/MRI scanner followed by 3 cycles of chemohormonal therapy (NCT03358563). Repeat PSMA PET/MRI was performed prior to prostatectomy and scans were interpreted by an experienced radiologist and nuclear medicine physician as complete response (CR), partial response (PR), no response (NR) or normal tissue. MRI scans were used to print a 3D mold of the prostate to allow PET and MRI directed mapping and microdissection of regions of interest from the resected prostate with slice-by-slice and lesion-to-lesion correlation. Cellular infiltrates were analyzed by flow cytometry in 3 to 5 tissue specimens per patient. Results: The frequency of CD8+ T cells in the total CD45+ infiltrate was highest in normal and CR areas and was significantly reduced in PR vs CR (p