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Progression of benign prostatic hyperplasia is associated with pro-inflammatory mediators and chronic activation of prostate-infiltrating lymphocytes
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2016 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 17, 23581-23593 p.Article in journal (Refereed) PublishedText
Abstract [en]

Benign prostatic hyperplasia (BPH) is a common chronic non-malignant condition whose prevalence substantially increases with age. Immune cell infiltration and pro-inflammatory mediators have been implicated in the pathogenesis. Here, we characterized 21 extracellular markers on prostate-infiltrating lymphocytes (PILs) and analyzed expression of 26 soluble proteins in prostate tissue obtained from BPH patients (n = 31). These data were correlated with clinical parameters and compared with peripheral blood mononuclear cells (PBMCs) (n = 10). Increased frequencies of T cells expressing co-inhibitory receptors LAG-3, PD-1, TIM-3 or CTLA-4, and co-stimulatory receptors CD28, OX40 or 4-1BB were observed in BPH tissue compared to PBMCs. These findings are consistent with chronic activation and possible functional exhaustion of PILs that may be further augmented by several identified pro-inflammatory factors, such as IL-8 and MCP-1, promoting inflammation and chemotaxis of immune cells to the prostate. Prostate size and plasma prostate-specific antigen levels positively correlated with IL-8 and MCP-1 concentrations, and frequencies of T cells expressing CTLA-4 and TIM-3. It remains to be established whether the link between inflammation and BPH progression supported by our findings reflects a progressive failure of the immune system leading to decreased immune surveillance and development of prostate cancer.

Place, publisher, year, edition, pages
Impact Journals LLC , 2016. Vol. 7, no 17, 23581-23593 p.
Keyword [en]
benign prostatic hyperplasia, prostate-infiltrating lymphocytes, immunophenotyping, cytokine/chemokine profiling, inflammation
National Category
Immunology in the medical area
URN: urn:nbn:se:kth:diva-189696DOI: 10.18632/oncotarget.8051ISI: 000377706200047ScopusID: 2-s2.0-84966549651OAI: diva2:948301
Swedish Research CouncilSwedish Foundation for Strategic Research

QC 20160711

Available from: 2016-07-11 Created: 2016-07-11 Last updated: 2016-07-11Bibliographically approved

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