Abstract B033: Probing the role of hypoxia and the tumor microenvironment at spatially resolved single cell resolution in prostate cancer disease trajectories

Prostate cancer (PCa) is the second most common cancer in men. Most patients will not develop aggressive disease, and a main challenge is to distinguish those patients that can be put on surveillance strategies from those that require definite treatment. Identifying robust prognostic and predictive biomarkers from tumor biopsies have been challenging due to the intra-tumor heterogeneity (ITH) and long life-history of the disease. Several components of the tumor micro-environment (TME) have been associated with shorter time to biochemical relapse and time to metastasis, but these analyses have mostly been based on single sample analysis, thus neglecting the high degree of ITH in PCa. Here, we performed pathology-guided 3D spatial sampling of PCa, followed by multi-layered genomic and transcriptomic profiling. Using single-cell sequencing from multiple distinct areas from each patient, we find both genomic, transcriptional and cellular ITH. We identify “pockets” of the tumor associated with markers of hypoxia and oxidative phosphorylation, and that these are associated with specific tumor and stromal cell-types. Using copy-number based analysis, our data reveal clonal evolution patterns at the single-cell level, pointing towards the earliest clonal populations, and our data supports an interplay between clonal evolution and tumor-promoting TMEs. Citation Format: Migle Mikutenaite, Evdoxia Karadoulama, Ronald Simon, Sarah Minner, Robert Bristow, Guido Sauter, Thorsten Schlomm, Joachim L. Weischenfeldt. Probing the role of hypoxia and the tumor microenvironment at spatially resolved single cell resolution in prostate cancer disease trajectories [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B033.