目的 介绍放射治疗(RT)对肿瘤免疫治疗调控机制,总结RT联合抗程序性死亡受体1(PD-1)和程序性死亡受体-配体1(PD-L1)为代表的免疫检查点抑制剂(ICIs)在基础和临床中的研究.方法 以"programmed cell death protein 1、PD-1 ligand 1、radiation therapy"为关键词,检索 PubMed 数据库 2013-01-31-2024-01-31 发表的相关文献.纳入标准:(1)RT调控肿瘤免疫治疗的基础研究;(2)RT联合抗PD-1/PD-L1治疗肿瘤的相关基础研究和临床试验;(3)联合治疗相关不良反应临床试验.排除标准:(1)研究机制模糊文献;(2)数据陈旧或会议、评论文献;(3)内容相似或重复文章.最终纳入61篇文献.结果 多项临床前研究和临床试验已证实,RT对肿瘤免疫治疗具有双向调控作用.RT可增强全身抗肿瘤免疫反应,使免疫"冷"肿瘤对PD-1/PD-L1阻断疗法更加敏感.研究表明,PD-1/PD-L1阻断疗法与RT联合,可能比传统的RT或单独的免疫治疗更具优势.但是,临床应用中二者联合的最佳顺序和时机仍存在较大争议.同时,RT因剂量和分割模式的不同,其联合免疫治疗将会带来不同的疗效.因此,为了产生有效的抗肿瘤免疫反应,RT联合PD-1/PD-L1抑制剂组合的最佳方案还有待深入研究.结论 RT调控肿瘤免疫微环境改变的机制较为复杂,对RT联合PD-1/PD-L1阻断疗法相关基础和临床研究的总结将为选择和优化此联合治疗方案并克服癌症免疫疗法的耐药性提供新思路和新策略.
Modulation of tumor immunity by radiotherapy and combined PD-1/PD-L1 inhibitors:from basics to clinical practice
Objective To introduce the mechanism of tumor immunotherapy modulation by radiation therapy(RT),and to summarize the research of RT combined with anti-programmed cell death protein 1(PD-1)/PD ligand 1(PD-L1)as repre-sentative of immune checkpoint inhibitors(ICIs)therapy in both basic and clinical settings.Methods Using"programmed cell death protein 1,PD ligand 1,radiation therapy"as keywords,relevant literatures published in PubMed database from January 31,2013 to January 31,2024 were searched.Inclusion criteria:(1)Research on the mechanism of tumor immu-notherapy regulated by RT;(2)Basic research and clinical trials related to the combination of RT with anti-PD-1/PD-L1 for tumor treatment;(3)Clinical trials on the adverse effects related to the combination therapy.Exclusion criteria:(1)Literature with unclear research mechanism;(2)Literature with outdated data or conferences,reviews;(3)Articles with similar content or duplicate articles.Finally,a total of 61 literature were included.Results RT can boost systemic anti-tumor immune responses and sensitized immunologically"cold"tumors to anti-PD-1/PD-L1 blockade.Research shows that anti-PD-1/PD-L1 blockade in combination with RT may provide a survival advantage over conventional RT or immu-notherapy alone.However,the treatment sequence and timing of the optimal combination strategies remain controversial.Meanwhile,RT in combination with immunotherapy will have variable efficacy depending on the dose and segmentation pattern.Therefore,the optimal regimen of RT in combination with PD-1/PD-L1 inhibitor combinations to generate an ef-fective anti-tumor immune response remains to be thoroughly investigated.Conclusions The mechanisms by which RT modulates the alteration of the tumor immune microenvironment are more complex,and a summary of basic and clinical studies related to RT in combination with PD-1/PD-L1 blockade therapy will provide new ideas and strategies for selecting and optimizing this combination regimen and overcoming resistance to cancer immunotherapy.
radiation therapyregulatory mechanismsPD-1/PD-L1 inhibitorscombination therapyreview literature
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