Multiplex imaging of localized prostate tumors reveals altered spatial organization of AR-positive cells in the microenvironment
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
Affiliations
Çiğdem Ak
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
Zeynep Sayar
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
Guillaume Thibault
Department of Biomedical Engineering, School of Medicine, OHSU, Portland, OR 97209, USA
Erik A. Burlingame
Department of Biomedical Engineering, School of Medicine, OHSU, Portland, OR 97209, USA
M.J. Kuykendall
Cancer Early Detection Advanced Research (CEDAR), Knight Cancer Institute, OHSU, Portland, OR 97239, USA
Jennifer Eng
Department of Biomedical Engineering, School of Medicine, OHSU, Portland, OR 97209, USA
Alex Chitsazan
Cancer Early Detection Advanced Research (CEDAR), Knight Cancer Institute, OHSU, Portland, OR 97239, USA
Koei Chin
Cancer Early Detection Advanced Research (CEDAR), Knight Cancer Institute, OHSU, Portland, OR 97239, USA
Andrew C. Adey
Cancer Early Detection Advanced Research (CEDAR), Knight Cancer Institute, OHSU, Portland, OR 97239, USA; Department of Molecular and Medical Genetics, Knight Cancer Institute, OHSU, Portland, OR 97239, USA
Christopher Boniface
Cancer Early Detection Advanced Research (CEDAR), Knight Cancer Institute, OHSU, Portland, OR 97239, USA
Paul T. Spellman
Cancer Early Detection Advanced Research (CEDAR), Knight Cancer Institute, OHSU, Portland, OR 97239, USA; Department of Molecular and Medical Genetics, Knight Cancer Institute, OHSU, Portland, OR 97239, USA
George V. Thomas
Cancer Early Detection Advanced Research (CEDAR), Knight Cancer Institute, OHSU, Portland, OR 97239, USA; Department of Pathology & Laboratory Medicine, School of Medicine, OHSU, Portland, OR 97239, USA
Ryan P. Kopp
Cancer Early Detection Advanced Research (CEDAR), Knight Cancer Institute, OHSU, Portland, OR 97239, USA; Department of Urology, School of Medicine, Knight Cancer Institute, Portland, OR 97239, USA
Emek Demir
Cancer Early Detection Advanced Research (CEDAR), Knight Cancer Institute, OHSU, Portland, OR 97239, USA; Division of Oncological Sciences, School of Medicine, OHSU, Portland, OR 97239, USA
Young Hwan Chang
Department of Biomedical Engineering, School of Medicine, OHSU, Portland, OR 97209, USA
Vasilis Stavrinides
Cancer Institute, University College London, London, UK
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; Corresponding author
Summary: 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.
