树突状细胞在前列腺肿瘤发生的早期阶段就开始编程非免疫原性的前列腺特异性T细胞反应。
Dendritic cells program non-immunogenic prostate-specific T cell responses beginning at early stages of prostate tumorigenesis.
作者信息
Mihalyo Marianne A, Hagymasi Adam T, Slaiby Aaron M, Nevius Erin E, Adler Adam J
机构信息
Center for Immunotherapy of Cancer and Infectious Diseases and Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
出版信息
Prostate. 2007 Apr 1;67(5):536-46. doi: 10.1002/pros.20549.
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.
背景
前列腺癌促进T细胞对前列腺抗原产生耐受性，这可能会限制针对这些抗原的前列腺癌疫苗的疗效。在此，我们试图确定T细胞耐受性产生时疾病进展的阶段，以及稳态树突状细胞（DC）和CD4(+)CD25(+) T调节细胞（Tregs）在诱导耐受性中的作用。
方法
将幼稚的HA特异性CD4(+) T细胞过继转移到Pro-HA x TRAMP转基因小鼠中后，分析其反应，这些小鼠在两种遗传背景上携带不同分期的表达HA的前列腺肿瘤，这两种背景显示出不同的肿瘤发生模式和动力学。通过清除法评估DC和Tregs在调节HA特异性CD4细胞反应中的作用。
结果
在两种遗传背景的肿瘤发生的所有阶段，HA特异性CD4细胞均发生非免疫原性反应。这些反应完全依赖于DC，但不受Tregs的明显影响。
结论
这些结果表明，耐受性是前列腺肿瘤的一种早期和普遍特性。
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