Prostate Atrophy, but Not Prostate Carcinoma, Is Characterised by a Relative Infiltration of Tregs
B Gurel, A Valdman, L Cappelli, K Tsilidis, J Hicks, AM De Marzo, CG Drake, AK Meeker. The Johns Hopkins University School of Medicine, Baltimore, MD; The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
Background: Regulatory T cells (Treg), a subset of CD4+ lymphocytes are thought to control tolerance to self-antigens and tumor-antigens, possibly acting by inhibiting the function of CD8+ (killer) T lymphocytes. Increased Treg have been reported in various malignancies, suggesting that Treg may facilitate tumor evasion from the immune response.
Design: The transcription factor Foxp3 is a specific immunohistochemical marker of Treg. We investigated the distribution of Foxp3+, CD4+ and CD8+ T cells using 4 tissue microarrays containing 1480 matched normal, atrophic and neoplastic prostate tissue samples from radical prostatectomies.
Results: CD4+ and CD8+ cells were increased in both atrophy and cancer compared to normal, denoting an increased inflammatory cell component in both pathologies. The CD4/CD8 ratio was inverted in normal prostate tissue. The CD4/CD8 ratio in atrophy was markedly different than in normal, PIN or cancer, approaching a more normal ratio. Foxp3+ cells were also significantly increased in atrophy. The Foxp3/CD8 ratio was increased in atrophy (mean 25.30, median 19.80), as compared to normal prostate (mean 14.43, median 9.45), but was not markedly increased in prostate cancer, contrary to what was expected. No correlation between Foxp3/CD8 ratio and Gleason score or tumor grade was found.
Conclusions: Our results contradict previous data suggesting a role for Treg in prostate tumor progression. Here, we did not observe an increased ratio of Treg/CD8 in prostate cancer. We found T cell infiltrates in the prostate gland biased towards CD8 T cells, regardless of the presence or absence of tumor. A marked elevation of Treg was found in atrophy as compared to normal, both absolute and relative to CD8+ lymphocytes. These data show that proliferative inflammatory atrophy (PIA) represents a unique immunological state, with an inversion in the expected CD4/CD8 ratio and a marked Treg infiltrate. This implies that PIA is characterized by an ongoing and tightly regulated immune response, a finding supported by recent data showing clonal populations of CD8 T cells in the prostate gland.
Category: Genitourinary (including renal tumors)
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 100, Wednesday Morning