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

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 mouse prostates, a model that closely recapitulates human PCa. PCa in PTEN 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.