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Phenotypic Analysis of Prostate-Infiltrating Lymphocytes Reveals T sub(H)17 and T sub(reg) Skewing

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

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Bibliographic Details
Published in:Clinical cancer research 2008-06, Vol.14 (11), p.3254-3261
Main Authors: Sfanos, Karen Sandell, Bruno, Tullia C, Maris, Charles H, Xu, Lauren, Thoburn, Christopher J, DeMarzo, Angelo M, Meeker, Alan K, Isaacs, William B, Drake, Charles G
Format: Article
Language:English
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Summary:PURPOSE: Pathologic examination of prostate glands removed from patients with prostate cancer commonly reveals infiltrating CD4 super(+) and CD8 super(+) 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 super(+) 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 super(+), CD25 super(+), GITR super(+)) was compared with naive, peripheral blood T cells using microarray analysis. RESULTS: CD4 super(+) PIL showed a paucity of T sub(H)2 (interleukin-4-secreting) cells, a surprising finding given the generally accepted association of these cells with chronic, smoldering inflammation. Instead, CD4 super(+) PIL seemed to be skewed towards a regulatory T sub(reg) phenotype (FoxP3 super(+)) as well as towards the T sub(H)17 phenotype (interleukin-17 super(+)). We also found that a preponderance of T sub(H)17-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 sub(reg) revealed expected T sub(reg)-associated transcripts (FoxP3, CTLA-4, GITR, LAG-3) as well as a number of unique cell surface markers that may serve as additional T sub(reg) markers. CONCLUSION: Taken together, these data suggest that T sub(H)17 and/or T sub(reg) CD4 super(+) T cells (rather than T sub(H)2 T cells) may be involved in the development or progression of prostate cancer.
ISSN:1078-0432
1557-3265