Transcriptome sequencing and multi-plex imaging of prostate cancer microenvironment reveals a dominant role for monocytic cells in progression

前列腺癌微环境的转录组测序和多重成像揭示了单核细胞在进展中的主导作用

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作者:Stefano Mangiola, Patrick McCoy, Martin Modrak, Fernando Souza-Fonseca-Guimaraes, Daniel Blashki, Ryan Stuchbery, Simon P Keam, Michael Kerger, Ken Chow, Chayanica Nasa, Melanie Le Page, Natalie Lister, Simon Monard, Justin Peters, Phil Dundee, Scott G Williams, Anthony J Costello, Paul J Neeson, Bh

Background

Prostate cancer is caused by genomic aberrations in normal epithelial cells, however clinical translation of findings from analyses of cancer cells alone has been very limited. A deeper understanding of the tumour microenvironment is needed to identify the key drivers of disease progression and reveal novel therapeutic opportunities.

Conclusions

This study advances our knowledge concerning the role of monocyte-derived recruitment in primary prostate cancer, and supports their key role in disease progression, patient survival and prostate microenvironment immune modulation.

Results

In this study, the experimental enrichment of selected cell-types, the development of a Bayesian inference model for continuous differential transcript abundance, and multiplex immunohistochemistry permitted us to define the transcriptional landscape of the prostate cancer microenvironment along the disease progression axis. An important role of monocytes and macrophages in prostate cancer progression and disease recurrence was uncovered, supported by both transcriptional landscape findings and by differential tissue composition analyses. These findings were corroborated and validated by spatial analyses at the single-cell level using multiplex immunohistochemistry. Conclusions: This study advances our knowledge concerning the role of monocyte-derived recruitment in primary prostate cancer, and supports their key role in disease progression, patient survival and prostate microenvironment immune modulation.

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