内源性前列腺癌特异性 CD8 T 细胞在小鼠 TCR 转基因模型中的抗肿瘤作用。
Anti-tumor effects of endogenous prostate cancer-specific CD8 T cells in a murine TCR transgenic model.
机构信息
Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
出版信息
Prostate. 2012 Apr;72(5):514-22. doi: 10.1002/pros.21453. Epub 2011 Jul 14.
BACKGROUND
The CD8 T-cell response to prostate and other cancers is often functionally diminished or absent. This may occur via deletion of tumor-specific T cells, through acquisition of an anergic phenotype, or via active suppression mediated by another population of cells.
METHODS
We used a double transgenic model in which mice express CD8 T cells specific for a prostate/prostate cancer antigen to study the response of CD8 T cells to evolving autochronous prostate tumors in TRAMP mice. CD8 T cells were analyzed for functionality by measuring IFN-γ production via flow cytometry and via an in vivo CTL killing assay. In addition, pathological scoring of the prostates of the double transgenic mice was compared to scoring of tumor burden prostates of ProTRAMP mice.
RESULTS
Tumor-specific CD8 T cells were not grossly deleted in these animals, but evidenced a clearly non-functional phenotype. Interestingly, full lytic function was rapidly recovered upon removal from tumor-bearing mice.
CONCLUSIONS
These data indicate a role for continuous antigen exposure in the maintenance of tumor-specific CD8 T-cell tolerance to prostate cancer.
背景
针对前列腺癌和其他癌症的 CD8 T 细胞反应通常功能降低或不存在。这可能是通过肿瘤特异性 T 细胞的缺失、获得无反应性表型，或通过另一群细胞介导的主动抑制来实现的。
方法
我们使用了一种双转基因模型，该模型中表达了针对前列腺/前列腺癌抗原的 CD8 T 细胞，以研究 CD8 T 细胞对 TRAMP 小鼠中不断发展的自主前列腺肿瘤的反应。通过流式细胞术和体内 CTL 杀伤测定来测量 IFN-γ 的产生，从而分析 CD8 T 细胞的功能。此外，还比较了双转基因小鼠的前列腺的病理评分与 ProTRAMP 小鼠的肿瘤负担前列腺的评分。
结果
在这些动物中，肿瘤特异性 CD8 T 细胞没有大量缺失，但表现出明显的无功能表型。有趣的是，在从荷瘤小鼠中移除后，完全的溶细胞功能迅速恢复。
结论
这些数据表明，持续的抗原暴露在维持前列腺癌的肿瘤特异性 CD8 T 细胞耐受中起作用。
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