Gunderson Andrew J, Young Kristina H
Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, Oregon.
Radiation Oncology Division, The Oregon Clinic, Portland, Oregon.
Adv Radiat Oncol. 2018 Oct 23;3(4):494-505. doi: 10.1016/j.adro.2018.07.005. eCollection 2018 Oct-Dec.
The purpose of this article is to assemble, review, and provide a synopsis of the historical and current literature regarding optimal sequencing of radiation (RT) and immunotherapy combination treatments.
A review of the literature was performed using PubMed with the query "radiation" and "Immunotherapy", "PD1", "PDL1", "CTLA4", "OX40", "checkpoint", "vaccine", "macrophage", "STING", and "TGFbeta". Studies that included sequencing of therapy were evaluated and the studies were included at the authors discretion.
A paucity of primary literature exists examining the best order of radiation and immunotherapy, most of which was performed in the pre-clinical setting. The observations are that optimal sequencing of various radiation plus immune therapy combinations is dependent on the mechanism(s) of activation by the combination treatment. Immunosuppressive molecules tend to be better inhibited prior to RT while engagement of costimulatory genes is better activated concomitantly with RT.
These data should compel more basic research into both the direct investigation of sequencing efficacy and studies on the mechanisms of immune mediated cell death potentiated by radio-therapy.
本文旨在汇总、回顾并概述关于放疗（RT）与免疫治疗联合治疗的最佳顺序的历史和当前文献。
使用PubMed对文献进行综述，检索词为“放疗”、“免疫治疗”、“PD1”、“PDL1”、“CTLA4”、“OX40”、“检查点”、“疫苗”、“巨噬细胞”、“STING”和“TGFβ”。对纳入治疗顺序的研究进行评估，研究纳入由作者自行决定。
关于放疗和免疫治疗最佳顺序的基础文献较少，其中大部分是在临床前环境中进行的。观察结果表明，各种放疗加免疫治疗组合的最佳顺序取决于联合治疗的激活机制。免疫抑制分子在放疗前往往能得到更好的抑制，而共刺激基因的激活在放疗时能得到更好的促进。
这些数据应促使更多基础研究直接探究顺序疗效，并研究放疗增强免疫介导细胞死亡的机制。
