Tumor cure by radiation therapy and checkpoint inhibitors depends on pre-existing immunity.

Tumor cure by radiation therapy and checkpoint inhibitors depends on pre-existing immunity.
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DOI:
10.1038/s41598-018-25482-w
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发表时间:
2018-05-03
期刊:
影响因子:
4.6
通讯作者:
Gough MJ
Gough MJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Crittenden MR;Zebertavage L;Kramer G;Bambina S;Friedman D;Troesch V;Blair T;Baird JR;Alice A;Gough MJ

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放射治疗是肿瘤抗原释放的来源,其具有充当内源性肿瘤疫苗接种事件的潜力。在临床前模型中,放射疗法与检查点抑制剂协同作用,通过CD8 T细胞应答治愈肿瘤。为了评估放射治疗引发的免疫应答,我们使用了一系列方法来阻断肿瘤植入引发的预先存在的免疫应答伪影。我们证明,在肿瘤植入时阻断免疫反应会阻断肿瘤驻留抗原特异性T细胞群的发展,并阻止通过放射疗法结合检查点免疫疗法治愈肿瘤。这些数据表明,这种治疗组合依赖于预先存在的免疫应答来治愈肿瘤,并且可能不是没有预先存在的免疫力的患者的解决方案。
Radiation therapy is a source of tumor antigen release that has the potential to serve as an endogenous tumor vaccination event. In preclinical models radiation therapy synergizes with checkpoint inhibitors to cure tumors via CD8 T cell responses. To evaluate the immune response initiated by radiation therapy, we used a range of approaches to block the pre-existing immune response artifact initiated by tumor implantation. We demonstrate that blocking immune responses at tumor implantation blocks development of a tumor-resident antigen specific T cell population and prevents tumor cure by radiation therapy combined with checkpoint immunotherapy. These data demonstrate that this treatment combination relies on a pre-existing immune response to cure tumors, and may not be a solution for patients without pre-existing immunity.
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