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Clin Cancer Res. 2008 Jun 1;14(11):3254-61. doi: 10.1158/1078-0432.CCR-07-5164.

Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing.

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  • 1Department of Urology, James Buchanan Brady Urological Institute, MD, USA.

Abstract

PURPOSE:

Pathologic examination of prostate glands removed from patients with prostate cancer commonly reveals infiltrating CD4+ and CD8+ T cells. Little is known about the phenotype of these cells, despite accumulating evidence suggesting a potential role for chronic inflammation in the etiology of prostate cancer.

EXPERIMENTAL DESIGN:

We developed a technique that samples the majority of the peripheral prostate through serial needle aspirates. CD4+ prostate-infiltrating lymphocytes (PIL) were isolated using magnetic beads and analyzed for subset skewing using both flow cytometry and quantitative reverse transcription-PCR. The transcriptional profile of fluorescence-activated cell sorted prostate-infiltrating regulatory T cells (CD4+, CD25+, GITR+) was compared with naïve, peripheral blood T cells using microarray analysis.

RESULTS:

CD4+ PIL showed a paucity of TH2 (interleukin-4-secreting) cells, a surprising finding given the generally accepted association of these cells with chronic, smoldering inflammation. Instead, CD4+ PIL seemed to be skewed towards a regulatory Treg phenotype (FoxP3+) as well as towards the TH17 phenotype (interleukin-17+). We also found that a preponderance of TH17-mediated inflammation was associated with a lower pathologic Gleason score. These protein level data were reflected at the message level, as analyzed by quantitative reverse transcription-PCR. Microarray analysis of pooled prostate-infiltrating T(reg) revealed expected Treg-associated transcripts (FoxP3, CTLA-4, GITR, LAG-3) as well as a number of unique cell surface markers that may serve as additional Treg markers.

CONCLUSION:

Taken together, these data suggest that TH17 and/or Treg CD4+ T cells (rather than TH2 T cells) may be involved in the development or progression of prostate cancer.

PMID:
18519750
[PubMed - indexed for MEDLINE]
PMCID:
PMC3082357
Free PMC Article
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