摘要
以免疫检查点抑制剂(ICIs)为主的免疫治疗改变了传统癌症治疗手段,但对于大多数类型的癌症,ICIs治疗受益十分有限(10%~30%),并且在某些癌症类型中基本无效(如胰腺癌、脑胶质瘤)。将ICIs治疗与现有及潜在的疗法相结合从而克服肿瘤原发性和获得性抵抗,对于提高治疗率、增加疗效的持久性和延长患者的生存期有重要意义。放射治疗能杀伤肿瘤细胞,同时引起促炎性分子的释放和免疫细胞的肿瘤浸润。此外,放射治疗能在肿瘤细胞中诱导产生微核,从而激活胞质核酸感应器,其中最重要的是环GMP-AMP合成酶-干扰素诱导基因通路,并且所产生的炎性反应信号效应重塑了肿瘤免疫微环境。肿瘤细胞在放射处理后还可通过新抗原的表达来影响免疫监测。本文将深入探讨放射治疗对于肿瘤微环境的免疫调节作用以及放疗与ICIs联合治疗作为一种潜在的癌症治疗策略,并介绍放射治疗引起的肿瘤微环境的重塑,包括对树突状细胞、T细胞浸润以及抑制性髓样细胞群的影响。
Immune checkpoint inhibitors(ICIs)-based tumor immunotherapy has changed the traditional cancer treatment.However,ICI treatment benefits small percentage of patients in most types of cancer(10%-30%),and is basically ineffective in some cancers(such as pancreatic cancer and glioma).Combining ICIs with existing and potential therapies to overcome tumor innate and acquired resistance is of great significance for improving the treatment efficacy,increasing the durability of the therapeutic effect and prolonging patients’survival.Radiotherapy can not only kill tumor cells,but also cause the release of pro-inflammatory molecules and immune cell infiltration in tumors.In addition,radiotherapy can induce micronuclei in tumor cells,thereby activating cytosolic DNA/RNA sensors,the most important of which is the cyclic GMP-AMP synthase(cGAS)-STING pathway.Radiotherapy can also regulate immune surveillance through the expression of tumor neoantigens.In this review,we will discuss in depth the immunomodulatory effect of radiotherapy on the tumor microenvironment and its combination with ICI as a potential cancer treatment,and focus on the effects of radiotherapy on non-tumor cells in the tumor microenvironment,including dendritic cells,T cell infiltration,as well as myeloid-derived suppressor cells.
作者
张强
吴邵雅
张靖
ZHANG Qiang;WU Shaoya;ZHANG Jing(Department of Radiation Oncology,University of Michigan,Ann Arbor,Michigan 48109,USA;College of Life Science and Technology of Huazhong Agricultural University,Wuhan 430070,China;Department of 1st Thoracic Medical Oncology,Hubei Cancer Hospital,Wuhan 430079,China)
出处
《肿瘤防治研究》
CAS
CSCD
2021年第1期1-6,共6页
Cancer Research on Prevention and Treatment
关键词
放射治疗
肿瘤微环境
免疫治疗
Radiotherapy
Tumor microenvironment
Immunotherapy