Dendritic cells program non‐immunogenic prostate‐specific T cell responses beginning at early stages of prostate tumorigenesis

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Abstract
BACKGROUND Prostate cancer promotes the development of T cell tolerance towards prostatic antigens, potentially limiting the efficacy of prostate cancer vaccines targeting these antigens. Here, we sought to determine the stage of disease progression when T cell tolerance develops, as well as the role of steady state dendritic cells (DC) and CD4+CD25+ T regulatory cells (Tregs) in programming tolerance. METHODS The response of naïve HA‐specific CD4+ T cells were analyzed following adoptive transfer into Pro‐HA × TRAMP transgenic mice harboring variably‐staged HA‐expressing prostate tumors on two genetic backgrounds that display different patterns and kinetics of tumorigenesis. The role of DC and Tregs in programming HA‐specific CD4 cell responses were assessed via depletion. RESULTS HA‐specific CD4 cells underwent non‐immunogenic responses at all stages of tumorigenesis in both genetic backgrounds. These responses were completely dependent on DC, but not appreciably influenced by Tregs. CONCLUSIONS These results suggest that tolerogenicity is an early and general property of prostate tumors. Prostate 67: 536–546, 2007.

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