Multiplex imaging of localized prostate tumors reveals altered spatial organization of AR-positive cells in the microenvironment.

Mapping the spatial interactions of cancer, immune, and stromal cell states presents novel opportunities for patient stratification and for advancing immunotherapy. While single-cell studies revealed significant molecular heterogeneity in prostate cancer cells, the impact of spatial stromal cell heterogeneity remains poorly understood. Here, we used cyclic immunofluorescent imaging on whole-tissue sections to uncover novel spatial associations between cancer and stromal cells in low- and high-grade prostate tumors and tumor-adjacent normal tissues. Our results provide a spatial map of single cells and recurrent cellular neighborhoods in the prostate tumor microenvironment of treatment-naive patients. We report unique populations of mast cells that show distinct spatial associations with M2 macrophages and regulatory T cells. Our results show disease-specific neighborhoods that are primarily driven by androgen receptor-positive (AR+) stromal cells and identify inflammatory gene networks active in AR+ prostate stroma.

iScience. 2024 Aug 03*** epublish ***

Çiğdem Ak, Zeynep Sayar, Guillaume Thibault, Erik A Burlingame, M J Kuykendall, Jennifer Eng, Alex Chitsazan, Koei Chin, Andrew C Adey, Christopher Boniface, Paul T Spellman, George V Thomas, Ryan P Kopp, Emek Demir, Young Hwan Chang, Vasilis Stavrinides, Sebnem Ece Eksi

Cancer Early Detection Advanced Research (CEDAR), Knight Cancer Institute, OHSU, Portland, OR 97239, USA., Department of Biomedical Engineering, School of Medicine, OHSU, Portland, OR 97209, USA., Cancer Institute, University College London, London, UK.