Characterization of the immune landscape in healthy mouse prostate and during prostate cancer progression

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Abstract
The immune landscape of healthy prostate and its alterations during prostate cancer (PCa) progression remain poorly characterized. Using scRNA-sequencing and multiparametric flow-cytometry analysis, we comprehensively characterized immune cells in wild-type and PTEN(i)pe-/- mouse prostates, a model that closely recapitulates human PCa. PCa in PTEN(i)pe-/- is marked by the recruitment of tumor-associated neutrophils (TANs), which represent the dominant immune cell population and resolved into eight distinct states, Trem2+ tumor-associated-macrophages (TAMs), and exhausted CD8+ T cells. Trem2+ TAMs differ from the three main resident macrophage populations in the healthy prostate, exhibiting a strong metabolic and immunosuppressive signature, likely driven by the MIF/HIF1A-signaling axis. This study provides the first detailed characterization of immune cells in the healthy mouse prostate and reveals changes in the immune landscape associated with prostate cancer progression.
Funding Information
  • Fondation ARC pour la Recherche sur le Cancer
  • INCA Région Sud, the Institute for Cancer Immunology (ICI) and Canceropôle
  • PHENOMIN (ANR-10-INBS-07)
  • European Research Council (787300)
  • Ministère de l’Enseignement Supérieur et de la Recherche
  • Fondation pour la Recherche Médicale
  • Fondation ARC pour la Recherche sur le Cancer
  • Institut National Du Cancer (INCA2019-191)
  • Institut for Cancer Immunology

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