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

• Published in: Cell reports (Cambridge) Vol. 37; no. 12; p. 110132
• Main Authors: Tuong, Zewen Kelvin, Loudon, Kevin W., Berry, Brendan, Richoz, Nathan, Jones, Julia, Tan, Xiao, Nguyen, Quan, George, Anne, Hori, Satoshi, Field, Sarah, Lynch, Andy G., Kania, Katarzyna, Coupland, Paul, Babbage, Anne, Grenfell, Richard, Barrett, Tristan, Warren, Anne Y., Gnanapragasam, Vincent, Massie, Charlie, Clatworthy, Menna R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.12.2021; Cell Press
• Subjects: Aged; Animals; Epithelial Cells - immunology; Epithelial Cells - metabolism; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; human prostate; Humans; immune landscape; macrophage; Macrophages - immunology; Macrophages - metabolism; Male; Mice; Mice, Inbred C57BL; Middle Aged; Prostate - immunology; Prostate - metabolism; prostate cancer; Prostatic Neoplasms - immunology; Prostatic Neoplasms - metabolism; Receptors, Androgen - metabolism; Resource; RNA-Seq; Single-Cell Analysis - methods; single-cell RNA sequencing; Transcriptome; zinc; Zinc - metabolism; single-cell RNA sequencing; macrophage; prostate cancer; immune landscape; human prostate; zinc
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2021.110132

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.