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

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 naive, peripheral blood T cells using microarray analysis. Results: CD4(+) PIL showed a paucity of T(H)2 (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 T-reg phenotype (FoxP3(+)) as well as towards the T(H)17 phenotype (interleukin-17(+)). We also found that a preponderance of T(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-reg revealed expected T-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-reg markers. Conclusion: Taken together, these data suggest that T(H)17 and/or T-reg CD4(+) T cells (rather than T(H)2 T cells) may be involved in the development or progression of prostate cancer.