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The inflammatory microenvironment and microbiome in prostate cancer development

Nature Reviews Urology volume 15, pages 11–24 (2018)Cite this article

Subjects

Key Points

  • Chronic inflammation is prevalent in the adult prostate and probably has a role in the formation of lesions that are putative risk factors for prostate cancer development

  • Prostatic inflammation might drive prostate carcinogenesis via oxidative stress and the generation of reactive oxygen species that induce mutagenesis or by causing epigenetic alterations that promote neoplastic transformation

  • Prostatic infection might drive an inflammatory prostate microenvironment, and the discovery of a urinary microbiome is probably important in terms of exposure of the prostate to potentially pathogenic microorganisms

  • Epithelial barrier disruption and inflammation in the prostate, once started, could establish a feed-forward mechanism resulting in a chronic, persistent inflammatory state

  • Full characterization of the link between the urinary microbiome and chronic prostatic inflammation might be critical to enable the development of strategies for prostate cancer prevention

Abstract

Chronic inflammation promotes the development of several types of solid cancers and might contribute to prostate carcinogenesis. This hypothesis partly originates in the frequent observation of inflammatory cells in the prostate microenvironment of adult men. Inflammation is associated with putative prostate cancer precursor lesions, termed proliferative inflammatory atrophy. Inflammation might drive prostate carcinogenesis via oxidative stress and generation of reactive oxygen species that induce mutagenesis. Additionally, inflammatory stress might cause epigenetic alterations that promote neoplastic transformation. Proliferative inflammatory atrophy is enriched for proliferative luminal epithelial cells of intermediate phenotype that might be prone to genomic alterations leading to prostatic intraepithelial neoplasia and prostate cancer. Studies in animals suggest that inflammatory changes in the prostate microenvironment contribute to reprogramming of prostate epithelial cells, a possible step in tumour initiation. Prostatic infection, concurrent with epithelial barrier disruption, might be a key driver of an inflammatory microenvironment; the discovery of a urinary microbiome indicates a potential source of frequent exposure of the prostate to a diverse number of microorganisms. Hence, current evidence suggests that inflammation and atrophy are involved in prostate carcinogenesis and suggests a role for the microbiome in establishing an inflammatory prostate microenvironment that might promote prostate cancer development and progression.

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Figure 1: Immune cell distribution in normal and inflamed prostate tissue.
Figure 2: Distribution and patterns of inflammation in the prostate.
Figure 3: Intermediate cells in prostatic proliferative inflammatory atrophy (PIA).
Figure 4: Prostate tissue with admixed benign, inflamed, and malignant areas.
Figure 5: Pathogenesis of prostatic inflammation caused by a breach of epithelial barrier function and invasion of microorganisms.

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Acknowledgements

The authors acknowledge the Prostate Cancer Foundation, the V Foundation for Cancer Research, the Patrick C. Walsh Prostate Cancer Research Fund, and the Department of Defense Prostate Cancer Research Program for ongoing research support.

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Authors and Affiliations

  1. Department of Pathology, Johns Hopkins University School of Medicine,

    Karen S. Sfanos, Srinivasan Yegnasubramanian, William G. Nelson & Angelo M. De Marzo

  2. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, 1550 Orleans Street, Baltimore, 21231, Maryland, USA

    Karen S. Sfanos, Srinivasan Yegnasubramanian, William G. Nelson & Angelo M. De Marzo

  3. Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, 21287, Maryland, USA

    Karen S. Sfanos, William G. Nelson & Angelo M. De Marzo

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  1. Karen S. Sfanos
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Contributions

K.S.S. and A.M.D. researched data for the article. K.S.S., S.Y., and A.M.D. wrote the manuscript. All authors made substantial contributions to discussion of the article content and reviewed and/or edited the manuscript before submission.

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Correspondence to Karen S. Sfanos or Angelo M. De Marzo.

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Sfanos, K., Yegnasubramanian, S., Nelson, W. et al. The inflammatory microenvironment and microbiome in prostate cancer development. Nat Rev Urol 15, 11–24 (2018). https://doi.org/10.1038/nrurol.2017.167

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