放疗联合免疫治疗机制及临床研究进展

Advances in mechanism and overview of clinical trials of combined radiotherapy and immunotherapy

目的放疗能促进肿瘤抗原呈递并引发免疫介导的抗肿瘤反应,放疗与免疫治疗联合可增强抗肿瘤免疫效应。本研究总结分析放疗联合免疫治疗的机制及近几年临床研究方面的进展。方法应用PubMed及中国期刊全文数据库(China National Knowledge Infrastructure,CNKI)检索系统,以"免疫治疗、免疫检查点抑制剂、程序性死亡分子/程序性死亡配体-1、T淋巴细胞相关抗原-4和放射治疗"为关键词,检索2014-01-01-2018-10-01相关文献。纳入标准:(1)放疗对免疫反应的影响;(2)免疫治疗的研究进展及耐药机制;(3)放疗联合免疫治疗的临床试验报道。排除标准:单一免疫治疗或放疗的临床试验。共筛选出文献47篇。结果放疗对免疫系统既有增强作用也有抑制作用,放疗分割模式及肿瘤类型影响免疫应答的改变。免疫治疗的耐药机制包括内在因素和外在因素两方面,与肿瘤细胞或免疫细胞的自身特征和肿瘤周围微环境有关。放疗联合免疫治疗在晚期恶性黑色素瘤、肺癌等实体瘤的临床试验中取得较好疗效,提高了疾病控制率,给部分患者带来生存获益。结论放疗与免疫治疗在生物学机制方面具有联合治疗的可行性,其广泛应用还有待于Ⅲ期临床试验结果。

OBJECTIVE Radiotherapy can promote the presentation of tumor antigen and induce immune-mediated anti-tumor response.Combination of radiotherapy and immunotherapy can enhance the anti-tumor immune effect.This article summarized and analyzed the mechanism of radiotherapy combined with immunotherapy and the progress of clinical research in recent years.METHODS PubMed and China National Knowledge Infrastructure(CNKI)were used to retrieve the relevant literatures from January 2014 to October 2018 with the keywords of "immunotherapy,immuno-checkpoint inhibitors,programmed death molecule/programmed death ligand-1,T lymphocyte associated antigen-4 and radiotherapy".Inclusion criteria:(1)the effect of radiotherapy on immune response;(2)the progress of immunotherapy and drug resistance mechanism;(3)the clinical trial report of radiotherapy combined with immunotherapy.Exclusion criteria:Clinical trials of single immunotherapy or radiotherapy.A total of 47 literatures were screened out.RESULTS Radiotherapy has both enhancement and inhibition effects on the immune system.Different doses and fractionation of radiotherapy and biological characteristics of tumors affect the changes of immune response.The mechanism of drug resistance in immunotherapy includes both internal and external factors,which are related to the characteristics of tumor cells or immune cells and the microenvironment.Radiotherapy combined with immunotherapy in the clinical trials of advanced malignant melanoma,lung cancer and other solid tumors has achieved good results,improved disease control rate,and brought survival benefits to some patients.CONCLUSION Radiotherapy combined with immunotherapy is feasible in biological mechanism,and its wide application still needs to be tested in phaseⅢclinical trials.