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Prostate. 2007 Apr 1;67(5):536-46.

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

Author information

1
Center for Immunotherapy of Cancer and Infectious Diseases and Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.

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 x 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.

PMID:
17221844
PMCID:
PMC2846359
DOI:
10.1002/pros.20549
[Indexed for MEDLINE]
Free PMC Article
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