Samstein Robert M, Riaz Nadeem
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Adv Radiat Oncol. 2018 Oct 23;3(4):527-533. doi: 10.1016/j.adro.2018.08.017. eCollection 2018 Oct-Dec.
Deficiencies in DNA damage repair (DDR) and response represent a common alteration in tumors, and exploitation of this feature using therapeutics has become more prominent.
Recent work has highlighted the important interaction between DDR defects, as well as DDR targeting agents such as radiation and the immunogenicity of the tumor. This relationship emphasizes the potential for combination therapeutics with immune checkpoint inhibitors (ICI). Somatic mutations and DDR defects are some of the strongest predictors of response to ICI.
This review highlights the interplay among DDR pathways, ionizing radiation, and ICI efficacy. The mechanisms of radiation immunogenicity, including the cytosolic DNA sensing cGAS/STING pathways, are also described.
A greater mechanistic understanding of the complex interaction between the DNA damage response and the immune system will expand the therapeutic potential of immunotherapy for patients with advanced cancer.
DNA损伤修复（DDR）和反应缺陷是肿瘤中常见的改变，利用治疗手段开发这一特性变得愈发突出。
近期研究强调了DDR缺陷之间的重要相互作用，以及诸如辐射等DDR靶向剂与肿瘤免疫原性之间的相互作用。这种关系凸显了联合使用免疫检查点抑制剂（ICI）进行治疗的潜力。体细胞突变和DDR缺陷是对ICI反应的一些最强预测指标。
本综述强调了DDR通路、电离辐射和ICI疗效之间的相互作用。还描述了辐射免疫原性的机制，包括胞质DNA传感cGAS/STING通路。
对DNA损伤反应与免疫系统之间复杂相互作用的更深入机制理解，将扩大免疫疗法对晚期癌症患者的治疗潜力。
