Resolving the immune landscape of human prostate at a single-cell level in health and cancer
Zewen Kelvin Tuong, Kevin W. Loudon, Brendan Berry, Nathan Richoz, Julia Jones, Xiao Tan, Quan Nguyen, Anne George, Satoshi Hori, Sarah Field, Andy G. Lynch, Katarzyna Kania, Paul Coupland, Anne Babbage, Richard Grenfell, Tristan Barrett, Anne Y. Warren, Vincent J. Gnanapragasam, Charlie E. Massie, Menna R. Clatworthy
Abstract
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.