双免疫联合治疗在晚期非小细胞肺癌中的一线应用

Dual Immunotherapy in Advanced Non-small Cell Lung Cancer:the Progress and Clinical Application

近年来,程序性死亡受体1(programmed death protein-1, PD-1)/程序性死亡配体1(programmed deathligand 1, PD-L1)抑制剂单药、PD-1抑制剂联合化疗日益广泛地用于非小细胞肺癌(non-small cell lung cancer, NSCLC)的一线治疗,但PD-L1低表达的患者治疗反应和生存获益有限,现有治疗方案尚不能完全满足真实世界患者的临床需求。因此,研究者们仍在探索新的有效或者高效的治疗方案,以求进一步提高NSCLC不同人群的疗效和生存预后。双免疫联合治疗,如PD-1抑制剂和细胞毒性T淋巴细胞相关抗原4(cytotoxic T lymphocyte associated antigen-4,CTLA-4)抑制剂联合在多种肿瘤中均显示出可观的长期生存获益,在NSCLC中亦显示出广阔的应用前景。除探索不同的新兴联合方案外,如何通过生物标志物准确识别最佳获益人群、如何通过多学科协作有效管理联合方案的安全性,也是双免疫联合治疗受关注的重点。本文就双免疫联合治疗的作用机制、研究进展、疗效预测标志物及未来探索方向等作一综述。

Programmed cell death protein-1(PD-1)/programmed cell death-ligand 1(PD-L1) inhibitors and PD-1 inhibitors plus chemotherapy combination regimens have been widely used in the first-line treatment of advanced nonsmall cell lung cancer(NSCLC),but patients with low PD-L1 expression have limited objective response and survival benefits.Existing treatment regimens are still difficult to fully meet the clinical needs of patients in the real world.Therefore,researchers are still exploring novel superactive treatment options to further improve the efficacy and survival prognosis of different subgroups in NSCLC.Dual immunotherapy [such as the combination of PD-1 and cytotoxic T lymphocyte associated antigen-4(CTLA-4) inhibitors] has shown considerable long-term survival benefits in a variety of tumors and has also shown broad clinical prospects in NSCLC.In addition to exploring different emerging combination options,how to accurately identify the optimal-benefit groups through predictive biomarkers and how to effectively manage the safety of combination immunotherapy through multidisciplinary collaboration are also the focus of dual immunotherapy.This article reviews the mechanism of action,research progress,predictive biomarkers and future exploration directions of dual immunotherapy.