Department of Histology and Embryology, Taishan Medical University, Taian, Shandong 271000, China.
Ningxia Human Stem Cell Institute, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China.
J Immunol Res. 2018 Aug 8;2018:6984948. doi: 10.1155/2018/6984948. eCollection 2018.
Lung cancer remains a leading cause of cancer-related mortality worldwide with the poor prognosis. Encouragingly, immune checkpoint blockade targeting programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) has dramatically changed the landscape for treatments in patients with non-small-cell lung cancer (NSCLC). However, only a small proportion of NSCLC patients responded to monotherapy of anti-PD-1/PDL1 agents; together, the development of resistance to anti-PD-1/PD-L1 therapy that leads to failure of anti-PD-1/PD-L1 therapy has significantly limited a broad applicability of the findings in clinical practices. Nowadays, several companion diagnostic assays for PDL1 expression have been introduced for identifying patients who may benefit the immunotherapy. In addition, results from clinical trials explored combinatory therapeutic strategies with conventional and/or targeted therapy reported a higher efficacy with an acceptable safety profile in NSCLC treatments, as compared to the monotherapy of these agents alone. In this review article, we summarized several anti-PD-1/PD-L1 agents licensed for NSCLC treatment, with a focus on predictive biomarkers and companion diagnostic assays for identification of NSCLC patients for immunotherapy anti-PD-1/PDL1 antibodies. Of a great interest, potentials of the combinatory therapy of anti-PD-1/PDL1 therapy with a conventional or targeted therapy, or other immunotherapy such as CAR-T cell therapy were emphasized in the article.
肺癌仍然是全球癌症相关死亡的主要原因,预后较差。令人鼓舞的是,针对程序性死亡受体 1(PD-1)和程序性死亡配体 1(PD-L1)的免疫检查点阻断已极大地改变了非小细胞肺癌(NSCLC)患者的治疗格局。然而,只有一小部分 NSCLC 患者对 PD-1/PDL1 单药治疗有反应;同时,抗 PD-1/PD-L1 治疗的耐药性的发展导致抗 PD-1/PD-L1 治疗的失败,这显著限制了这些发现在临床实践中的广泛适用性。如今,已经引入了几种用于检测 PDL1 表达的伴随诊断检测方法,以识别可能受益于免疫疗法的患者。此外,临床试验的结果探索了联合治疗策略,包括常规和/或靶向治疗,与这些药物的单药治疗相比,在 NSCLC 治疗中显示出更高的疗效和可接受的安全性。在这篇综述文章中,我们总结了几种已获批准用于 NSCLC 治疗的抗 PD-1/PD-L1 药物,重点介绍了预测生物标志物和伴随诊断检测方法,用于识别适合免疫治疗的 NSCLC 患者。值得关注的是,文章强调了抗 PD-1/PDL1 治疗与常规或靶向治疗联合治疗,或与 CAR-T 细胞疗法等其他免疫疗法联合治疗的潜力。