Dendritic cells program non-immunogenic prostate-specific T cell responses beginning at early stages of prostate tumorigenesis.
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.
Mihalyo
Marianne A
MA
Center for Immunotherapy of Cancer and Infectious Diseases and Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
Hagymasi
Adam T
AT
Slaiby
Aaron M
AM
Nevius
Erin E
EE
Adler
Adam J
AJ
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D006651:Histocytochemistry; D007700:Kinetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental; D009929:Organ Size; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
D000951:Antigens, Neoplasm; D053219:Receptors, Tumor Necrosis Factor, Member 25; C506034:Tnfrsf25 protein, mouse