Androgen ablation mitigates tolerance to a prostate/prostate cancer-restricted antigen
Androgen ablation mitigates tolerance to a prostate/prostate cancer-restricted antigen
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DOI：
10.1016/j.ccr.2005.01.027
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发表时间：
2005-03-01
期刊：
影响因子：
50.3
通讯作者：
Adler, AJ
中科院分区：
文献类型：
--
作者：
Drake, CG;Doody, ADH;Adler, AJ
为了了解 T 细胞对前列腺癌的反应，我们创建了以前列腺限制模式表达模型抗原的转基因小鼠，并将这些动物与发生自发性前列腺癌的 TRAMP 小鼠杂交。前列腺特异性 CD4 T 细胞的过继转移表明，在没有前列腺癌的情况下，前列腺大多被忽视。肿瘤发生允许T细胞识别前列腺，但这种识别是耐受性的，导致增殖失败并最终导致全身水平的低反应性。雄激素消除（转移性前列腺癌最常见的治疗方法）能够减轻这种耐受性，使前列腺特异性 T 细胞在疫苗接种后能够扩增并发展效应功能。这些结果表明，在雄激素消融后进行的前列腺癌免疫疗法可能最有效。
To understand the T cell response to prostate cancer, we created transgenic mice that express a model antigen in a prostate-restricted pattern and crossed these animals to TRAMP mice that develop spontaneous prostate cancer. Adoptive transfer of prostate-specific CD4 T cells shows that, in the absence of prostate cancer, the prostate gland is mostly ignored. Tumorigenesis allows T cell recognition of the prostate gland-but this recognition is tolerogenic, resulting in abortive proliferation and ultimately in hyporesponsiveness at the systemic level. Androgen ablation (the most common treatment for metastatic prostate cancer) was able to mitigate this tolerance-allowing prostate-specific T cells to expand and develop effector function after vaccination. These results suggest that immunotherapy for prostate cancer may be most efficacious when administered after androgen ablation.