Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, OR, 97213, USA.
The Oregon Clinic, Portland, OR, 97213, USA.
Sci Rep. 2018 May 3;8(1):7012. doi: 10.1038/s41598-018-25482-w.
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.
放射治疗是肿瘤抗原释放的一个来源，有可能作为内源性肿瘤疫苗接种事件。在临床前模型中，放射治疗与检查点抑制剂协同作用，通过 CD8 T 细胞反应治愈肿瘤。为了评估放射治疗引发的免疫反应，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反应假象。我们证明，在肿瘤植入时阻断免疫反应会阻止肿瘤驻留抗原特异性 T 细胞群的发展，并防止放射治疗联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反应来治愈肿瘤，对于没有预先存在免疫力的患者来说，可能不是一个解决方案。
