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. 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.

Bioinformatics Division The Walter and Eliza Hall Institute of Medical Research Parkville Victoria Australia

Cancer Program Biomedicine Discovery Institute Monash University Clayton Victoria Australia

Department of Anatomy and Developmental Biology Monash University Clayton Victoria Australia

Department of Medical Biology University of Melbourne Melbourne Victoria Australia

Department of Surgery The University of Melbourne Parkville Victoria Australia

Department of Urology Frankston Hospital Frankston Victoria Australia

Department of Urology Royal Melbourne Hospital Parkville Victoria Australia

Epworth Center of Cancer Research Clayton Victoria Australia

Flow Cytometry Facility The Walter and Eliza Hall Institute of Medical Research Parkville Victoria Australia

Institute of Microbiology of the Czech Academy of Sciences Prague Czech Republic

Peter MacCallum Cancer Centre Melbourne VIC 3000 Australia

School of Mathematics and Statistics University of Melbourne Melbourne VIC 3010 Australia

Sir Peter MacCallum Department of Oncology University of Melbourne Melbourne Victoria Australia

The Olivia Newton John Cancer Research Institute Heidelberg Melbourne Australia

The Peter Doherty Institute for Infection and Immunity Parkville Victoria Australia

University of Queensland Diamantina Institute Translational Research Institute University of Queensland Brisbane QLD Australia

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