In Vivo Imaging of an Inducible Oncogenic Tumor Antigen Visualizes Tumor Progression and Predicts CTL Tolerance
In Vivo Imaging of an Inducible Oncogenic Tumor Antigen Visualizes Tumor Progression and Predicts CTL Tolerance
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DOI：
10.4049/jimmunol.0900893
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发表时间：
2010-03-15
影响因子：
4.4
通讯作者：
Blankenstein, Thomas
中科院分区：
文献类型：
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作者：
Buschow, Christian;Charo, Jehad;Blankenstein, Thomas
通过无创成像可视化癌基因/肿瘤Ag的表达对于了解肿瘤的发展和治疗过程具有重要意义。我们建立了有条件表达SV40大T Ag和荧光素酶（TagLuc）融合蛋白的转基因（Tg）小鼠，在Cre重组酶介导的激活下，通过生物发光成像监测癌基因/肿瘤Ag的表达。独立于cre介导的重组，TagLuc基因在不同组织中的表达水平较低，可能是由于停止盒的泄漏。生物发光成像检测到的TagLuc自发表达水平在不同Tg系之间存在差异，这取决于Tg表达盒的性质，并与标签特异性CTL耐受性相关。肝特异性Cre-loxP位点介导切除分离启动子和TagLuc融合基因的停止盒后，观察肝细胞癌的发展情况。普遍存在的TagLue低水平表达导致转移效应T细胞不能排斥表达tag的肿瘤，而不是引起移植物抗宿主病。该模型可用于研究不同水平的耐受性，早期监测肿瘤发展，并快速可视化治疗干预的效果与正常组织中低水平Ag表达的潜在副作用。免疫学杂志，2010,18(4):2930-2938。
Visualizing oncogene/tumor Ag expression by noninvasive imaging is of great interest for understanding processes of tumor development and therapy. We established transgenic (Tg) mice conditionally expressing a fusion protein of the SV40 large T Ag and luciferase (TagLuc) that allows monitoring of oncogene/tumor Ag expression by bioluminescent imaging upon Cre recombinase-mediated activation. Independent of Cre-mediated recombination, the TagLuc gene was expressed at low levels in different tissues, probably due to the leakiness of the stop cassette. The level of spontaneous TagLuc expression, detected by bioluminescent imaging, varied between the different Tg lines, depended on the nature of the Tg expression cassette, and correlated with Tag-specific CTL tolerance. Following liver-specific Cre-loxP site-mediated excision of the stop cassette that separated the promoter from the TagLuc fusion gene, hepatocellular carcinoma development was visualized. The ubiquitous low level TagLue expression caused the failure of transferred effector T cells to reject Tag-expressing tumors rather than causing graft-versus-host disease. This model may be useful to study different levels of tolerance, monitor tumor development at an early stage, and rapidly visualize the efficacy of therapeutic intervention versus potential side effects of low-level Ag expression in normal tissues. The Journal of Immunology, 2010,184: 2930-2938.