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

Cell Rep

Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK; Cellular Genetics, Wellcome Sanger Institute, Hinxton, UK; NIHR Cambridge Biomedical Research Centre, Cambridge, UK; Cambridge Institute of Therapeutic Immunology & Infectious Diseases, Cambridge, UK. Electronic address:

Published: December 2021

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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721283PMC
http://dx.doi.org/10.1016/j.celrep.2021.110132DOI Listing

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