Generating antitumor immunity by targeted radiation therapy: Role of dose and fractionation.
Generating antitumor immunity by targeted radiation therapy: Role of dose and fractionation.
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DOI：
10.1016/j.adro.2018.08.021
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发表时间：
2018-10
影响因子：
2.3
通讯作者：
Formenti SC
中科院分区：
文献类型：
--
作者：
Ko EC;Benjamin KT;Formenti SC
越来越多的证据支持放射治疗在诱导抗肿瘤免疫中的作用。随着立体定向放射治疗的最新进展，人们越来越认识到，当与免疫检查点阻断联合使用时，所选择的辐射剂量类型和分离方案可能既影响局部肿瘤控制，也影响对全身控制很重要的免疫反应的产生。尽管在临床前和临床环境中已经测试了广泛的辐射剂量和分割模式，但最近的临床前证据表明，存在每分割剂量阈值，超过该阈值，辐射在产生肿瘤免疫反应方面的效果就会降低。这样的阈值似乎与肿瘤有关，可能反映了癌症的不同基因突变。在这篇综述中，我们讨论了关键的临床前和临床证据与辐射剂量和分离的考虑。未来的临床试验应侧重于确定最佳辐射剂量和分离时间表，这可能取决于临床情况。
Accumulating evidence supports the role of radiation therapy in the induction of antitumor immunity. With recent advancements in stereotactic radiation therapy, there is increasing appreciation that, when combined with immune checkpoint blockade, the type of radiation dose and fractionation regimen selected may both influence local tumor control and also affect the generation of immune responses that are important for systemic control. Although a broad range of radiation dose and fractionation schema have been tested in both the preclinical and clinical settings, recent preclinical evidence suggests the existence of a dose per fraction threshold beyond which radiation becomes less effective in generating tumor immune responses. Such a threshold seems to be tumor dependent, probably reflecting different genetic mutations of cancer. In this review we discuss the key preclinical and clinical evidence relating to radiation dose and fractionation considerations. Future clinical trials should focus on identifying optimal radiation dose and fractionation schedules, which may depend on the clinical context.