PD-L1和VEGF双靶点联合阻断治疗的研究进展  

Research Progress of Dual-target Blocking Therapy of PD-L1 and VEGF

作　　者：赵梦泽 李凤智 王鹏银 李剑 徐寒梅[1] ZHAO Meng-ze;LI Feng-zhi;WANG Peng-yin;LI Jian;XU Han-mei(Life Science and Technology College,China Pharmaceutical University,Nanjing 211100,China;Tasly Biopharmaceuticals Co.,Ltd.,Shanghai 201203,China)

机构地区：[1]中国药科大学生命科学与技术学院,南京211100 [2]天士力生物医药股份有限公司,上海201203

出　　处：《中国生物工程杂志》2021年第9期71-77,共7页China Biotechnology

摘　　要：免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)通过阻断负调控免疫信号激活宿主抗肿瘤免疫反应。临床试验表明,ICIs的治疗能够明显引起部分晚期癌症患者的肿瘤消退。在临床实践中,ICIs治疗的一个主要问题是药物应答率低。尽管PD-L1表达、错配修复缺陷、肿瘤浸润性淋巴细胞状态等多种预测生物标志物已被用于筛选对治疗有应答的患者,但ICIs单药治疗的耐药性仍存在。近期研究表明,联合抗VEGF治疗可以减轻ICIs的耐药性。VEGF能抑制肿瘤生长和转移所必需的血管生成,同时能够对肿瘤免疫微环境进行重编程,减轻ICIs的耐药性。目前已针对此双靶点的联合治疗开展了很多临床试验,并获得了令人振奋的结果。对抗PD-L1联合抗VEGF治疗的作用机制以及PD-L1/VEGF联合阻断治疗的临床研究进行了综述汇总。Immune checkpoint inhibitor(immune checkpoint inhibitors,ICIs)activates host anti-tumor immune response by blocking negative regulatory immune signals.Clinical trials have shown that the treatment of ICIs can significantly cause tumor regression in some patients with advanced cancer.In clinical practice,one of the main problems in ICIs treatment is the low response rate.Although various predictive biomarkers such as PDL1 expression,mismatch repair deficiency,and tumor-infiltrating lymphocyte status have been used to screen patients who respond to treatment,the resistance of ICIs monotherapy still exists.Recent studies have shown that combined anti-VEGF therapy can reduce the resistance of ICIs.VEGF can inhibit angiogenesis necessary for tumor growth and metastasis,while it can reprogram the tumor immune microenvironment and reduce the resistance of ICIs.Many clinical trials have been carried out for the combination therapy of these two targets,and exciting results have been obtained.The mechanism of action of anti-PD-L1 combined with anti-VEGF therapy and the clinical studies of PD-L1/VEGF combined blocking therapy were reviewed and summarized.

关 键 词：PD-L1 VEGF 肿瘤免疫微环境 

分 类 号：Q819[生物学—生物工程]