Abstract

Abstract Prostate cancer boasts a complex morphological structure and diverse cellular composition, yet current technology falls short in resolving the detailed spatial interactions among cells within the environment. In this study, we employed the Xenium platform, coupled with the 3D reconstruction tool Mushroom, to examine high-resolution spatial cellular interactions within the prostate cancer microenvironment. Our investigation focused on the transition of molecular characteristics from normal to high-grade prostatic intraepithelial neoplasia (HGPIN, pre-cancer), spanning the spectrum of Gleason Grades 3 to 4 and advancing to metastatic prostate cancer. We identified genes with unique spatial and grade-dependent expression profiles, including MYC, CP, and UHCL1. Evaluating sub-cellular imaging facilitated a comprehensive characterization and quantification of immune and stromal interactions, unveiling distinct spatial niches across transition stages. These findings underscore the nuanced immune interactions within the tumor microenvironment and offer crucial insights into the development of immunotherapeutic approaches tailored to the specific spatial and immune dynamics observed in advanced prostate cancer. This research contributes to the evolving understanding of prostate cancer progression, providing a foundation for the development of targeted therapies that disrupt specific cellular interactions. Citation Format: Chia-Kuei Mo, Reyka G. Jayasinghe, Ateih Abedin do, Xiang Li, Cody Weimholt, Eric H. Kim, Russell Pachynski, Feng Chen, Li Ding. Sub-cellular spatial resolution of immune and stromal interactions underlying prostate cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1147.

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