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

Abstract

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 T(H) 1 biased up to approximately 30 days, followed by a predominance of T(H) 17-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.