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

Cell Rep. 2021 Dec 21;37(12):110132. doi: 10.1016/j.celrep.2021.110132.

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.

Keywords: human prostate; immune landscape; macrophage; prostate cancer; single-cell RNA sequencing; zinc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism*
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Prostate / immunology*
  • Prostate / metabolism*
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / metabolism*
  • RNA-Seq
  • Receptors, Androgen / metabolism
  • Single-Cell Analysis / methods
  • Transcriptome*
  • Zinc / metabolism

Substances

  • Receptors, Androgen
  • Zinc