Dissection of prostate tumour, stroma and immune transcription reveals a key contribution by the microenvironment to disease progression

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. In this study, the experimental enrichment of selected cell-types and the development a Bayesian inference model for continuous differential transcript abundance analyses permitted definition of the transcriptional landscape of the prostate cancer microenvironment across the disease progression spectrum. An important role of monocytes and macrophages in prostate cancer progression and disease recurrence was reinforced by both our transcriptional landscape findings and by differential tissue composition analyses. This study contributes to understanding of monocyte-derived recruitment in primary prostate cancer, and supports a clear direction for further investigation into mechanisms of the immune system that contribute to disease progression.