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 Gnanapragasam; Charlie Massie; Menna R. Clatworthy

doi:10.1016/j.celrep.2021.110132

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 Gnanapragasam, Charlie Massie, Menna R. Clatworthy

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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.

Original language	English
Article number	110132
Number of pages	24
Journal	Cell Reports
Volume	37
Issue number	12
DOIs	https://doi.org/10.1016/j.celrep.2021.110132
Publication status	Published - 21 Dec 2021

Keywords

Single-cell RNA sequencing
Macrophage
Zinc
Immune landscape
Human prostate
Prostate cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Copyright 2021 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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Tuong, Z. K., Loudon, K. W., Berry, B., Richoz, N., Jones, J., Tan, X., Nguyen, Q., George, A., Hori, S., Field, S., Lynch, A. G., Kania, K., Coupland, P., Babbage, A., Grenfell, R., Barrett, T., Warren, A. Y., Gnanapragasam, V., Massie, C., & Clatworthy, M. R. (2021). Resolving the immune landscape of human prostate at a single-cell level in health and cancer. Cell Reports, 37(12), Article 110132. https://doi.org/10.1016/j.celrep.2021.110132

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

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 = "Single-cell RNA sequencing, Macrophage, Zinc, Immune landscape, Human prostate, Prostate cancer",

author = "Tuong, {Zewen Kelvin} and Loudon, {Kevin W.} and Brendan Berry and Nathan Richoz and Julia Jones and Xiao Tan and Quan Nguyen and Anne George and Satoshi Hori and Sarah Field and Lynch, {Andy G.} and Katarzyna Kania and Paul Coupland and Anne Babbage and Richard Grenfell and Tristan Barrett and Warren, {Anne Y.} and Vincent Gnanapragasam and Charlie Massie and Clatworthy, {Menna R.}",

note = "Z.K.T. and M.R.C. are supported by a Medical Research Council Human Cell Atlas Research Grant (MR/S035842/1), K.W.L is supported by a Kidney Research UK Clinical Training Fellowship (TF_013_20171124), N.R. was supported by a Wellcome Fellowship (106809/Z/15/Z), M.R.C. is supported by a Versus Arthritis Cure Challenge Research Grant (21777), and an NIHR Research Professorship (RP-2017-08-ST2-002). AYW is supported by the Cancer Research UK Cambridge Centre (C9685/A25177) and NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). Z.K.T. holds an honorary research fellow appointment with The University of Queensland Diamantina Institute. We are grateful for infrastructure support from the Cambridge NIHR Biomedical Campus and Cancer Research UK Cambridge Centre. The NIHR Cambridge Biomedical Research Centre (BRC) is a partnership between Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, funded by the National Institute for Health Research (NIHR). ",

year = "2021",

month = dec,

day = "21",

doi = "10.1016/j.celrep.2021.110132",

language = "English",

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journal = "Cell Reports",

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Tuong, ZK, Loudon, KW, Berry, B, Richoz, N, Jones, J, Tan, X, Nguyen, Q, George, A, Hori, S, Field, S, Lynch, AG, Kania, K, Coupland, P, Babbage, A, Grenfell, R, Barrett, T, Warren, AY, Gnanapragasam, V, Massie, C & Clatworthy, MR 2021, 'Resolving the immune landscape of human prostate at a single-cell level in health and cancer', Cell Reports, vol. 37, no. 12, 110132. https://doi.org/10.1016/j.celrep.2021.110132

TY - JOUR

T1 - Resolving the immune landscape of human prostate at a single-cell level in health and cancer

AU - Tuong, Zewen Kelvin

AU - Loudon, Kevin W.

AU - Berry, Brendan

AU - Richoz, Nathan

AU - Jones, Julia

AU - Tan, Xiao

AU - Nguyen, Quan

AU - George, Anne

AU - Hori, Satoshi

AU - Field, Sarah

AU - Lynch, Andy G.

AU - Kania, Katarzyna

AU - Coupland, Paul

AU - Babbage, Anne

AU - Grenfell, Richard

AU - Barrett, Tristan

AU - Warren, Anne Y.

AU - Gnanapragasam, Vincent

AU - Massie, Charlie

AU - Clatworthy, Menna R.

N1 - Z.K.T. and M.R.C. are supported by a Medical Research Council Human Cell Atlas Research Grant (MR/S035842/1), K.W.L is supported by a Kidney Research UK Clinical Training Fellowship (TF_013_20171124), N.R. was supported by a Wellcome Fellowship (106809/Z/15/Z), M.R.C. is supported by a Versus Arthritis Cure Challenge Research Grant (21777), and an NIHR Research Professorship (RP-2017-08-ST2-002). AYW is supported by the Cancer Research UK Cambridge Centre (C9685/A25177) and NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). Z.K.T. holds an honorary research fellow appointment with The University of Queensland Diamantina Institute. We are grateful for infrastructure support from the Cambridge NIHR Biomedical Campus and Cancer Research UK Cambridge Centre. The NIHR Cambridge Biomedical Research Centre (BRC) is a partnership between Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, funded by the National Institute for Health Research (NIHR).

PY - 2021/12/21

Y1 - 2021/12/21

N2 - 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.

AB - 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.

KW - Single-cell RNA sequencing

KW - Macrophage

KW - Zinc

KW - Immune landscape

KW - Human prostate

KW - Prostate cancer

U2 - 10.1016/j.celrep.2021.110132

DO - 10.1016/j.celrep.2021.110132

M3 - Article

SN - 2211-1247

VL - 37

JO - Cell Reports

JF - Cell Reports

IS - 12

M1 - 110132

ER -

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

Abstract

Keywords

UN SDGs

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