Phenotypic analysis of prostate-infiltrating lymphocytes reveals T H17 and Treg skewing

Karen Sandell Sfanos, Tullia C. Bruno, Charles H. Maris, Lauren Xu, Christopher J. Thoburn, Angelo M. Demarzo, Alan K. Meeker, William B. Isaacs, Charles G. Drake

Research output: Contribution to journalArticlepeer-review

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 Tcells using microarray analysis. Results: CD4+ PIL showed a paucity of T H2 (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 regulatoryTreg phenotype (FoxP3+) as well as towards theTH17 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 Treg 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 T reg markers. Conclusion: Taken together, these data suggest that TH17 and/orTreg CD4+ Tcells (rather than T H2 Tcells) may be involved in the development or progression of prostate cancer.

Original languageEnglish (US)
Pages (from-to)3254-3261
Number of pages8
JournalClinical Cancer Research
Volume14
Issue number11
DOIs
StatePublished - Jun 1 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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