4.4 Article

T cells localized to the androgen-deprived prostate are TH1 and TH17 biased

期刊

PROSTATE
卷 72, 期 11, 页码 1239-1247

出版社

WILEY
DOI: 10.1002/pros.22476

关键词

castration; inflammation; cytokine; prostate; rat

资金

  1. DOD [W81XWH-06-1-0184]
  2. NIH [T32 CA009135]

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BACKGROUND T cells infiltrate the prostates of prostate cancer patients undergoing neoadjuvant androgen deprivation. These prostate-infiltrating T cells have an oligoclonal phenotype, suggesting the development of an antigen-specific T-cell response. We hypothesized that androgen deprivation might elicit a prostate tissue-specific T-cell response that could potentially be combined with other immune-active therapies, and consequently sought to investigate the nature and timing of this T-cell response following castration. METHODS We investigated the phenotype and cytokine expression of T cells at various time points in the prostates of Lewis rats following surgical castration, and used adoptive transfer of prostate-infiltrating lymphocytes (PILs) to determine whether the infiltration by T cells was mediated by effects of castration on the prostate or lymphocytes. RESULTS Prostate T-cell infiltration shortly after castration was TH1 biased up to approximately 30 days, followed by a predominance of TH17-type cells, which persisted until at least 90 days post castration. PILs from sham-treated or castrate rats localized to the prostates of castrate animals. CONCLUSIONS These observations suggest castration elicits a time-dependent prostate-specific T-cell infiltration, and this infiltration is likely mediated by effects of castration on prostate tissue rather than T-cells. These findings have implications for the timing of immunotherapies combined with androgen deprivation as treatments for prostate cancer. Prostate 72:12391247, 2012. (C) 2011 Wiley Periodicals, Inc.

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