Resolving the immune landscape of human prostate at a single-cell level in health and cancer

The prostate gland produces prostatic fluid, high in zinc and citrate and essential for the maintenance of spermatozoa. Prostate cancer is a common condition with limited treatment efficacy in castration-resistant metastatic disease, including with immune checkpoint inhibitors. Using single-cell RNA-sequencing to perform an unbiased assessment of the cellular landscape of human prostate, we identify a subset of tumor-enriched androgen receptor-negative luminal epithelial cells with increased expression of cancer-associated genes. We also find a variety of innate and adaptive immune cells in normal prostate that were transcriptionally perturbed in prostate cancer. An exception is a prostate-specific, zinc transporter-expressing macrophage population (MAC-MT) that contributes to tissue zinc accumulation in homeostasis but shows enhanced inflammatory gene expression in tumors, including T cell-recruiting chemokines. Remarkably, enrichment of the MAC-MT signature in cancer biopsies is associated with improved disease-free survival, suggesting beneficial antitumor functions. [Display omitted] •An immune cell atlas of healthy human prostate and prostate cancer•Low androgen receptor-expressing luminal epithelial cell present in prostate cancer•Metallothionein-expressing macrophage subset (MAC-MT) regulates prostate zinc•MAC-MT gene signature in prostate cancer associated with better outcomes Tuong et al. generated a single-cell transcriptomic map of the human prostate immune landscape in health and show how this is perturbed in cancer. They identify a prostate-specific macrophage population that helps maintain tissue zinc and is associated with better outcomes in cancer.