Huang Zhangfeng, Su Wenhao, Lu Tong, Wang Yuanyong, Dong Yanting, Qin Yi, Liu Dahai, Sun Lili, Jiao Wenjie
Department of Thoracic Surgery, Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Ultrasound, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Front Pharmacol. 2020 Oct 7;11:578091. doi: 10.3389/fphar.2020.578091. eCollection 2020.
Lung cancer is one of the most common cancers and the leading cause of cancer-related deaths worldwide. Most of these patients with non-small cell lung cancer (NSCLC) present with the advanced stage of the disease at the time of diagnosis, and thus decrease the 5-year survival rate to about 5%. Immune checkpoint inhibitors (ICIs) can act on the inhibitory pathway of cancer immune response, thereby restoring and maintaining anti-tumor immunity. There are already ICIs targeting different pathways, including the programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) pathway. Since March 2015, the US Food and Drug Administration (FDA) approved nivolumab (anti-PD-1 antibody) as the second-line option for treatment of patients with advanced squamous NSCLC. Additionally, a series of inhibitors related to PD-1/PD-L1 immune-checkpoints have helped in the immunotherapy of NSCLC patients, and modified the original treatment model. However, controversies remain regarding the use of ICIs in a subgroup with targeted oncogene mutations is a problem that we need to solve. On the other hand, there are continuous efforts to find biomarkers that effectively predict the response of ICIs to screen suitable populations. In this review, we have reviewed the history of the continuous developments in cancer immunotherapy, summarized the mechanism of action of the immune-checkpoint pathways. Finally, based on the results of the first-line recent trials, we propose a potential first-line immunotherapeutic strategy for the treatment of the patients with NSCLC.
肺癌是最常见的癌症之一，也是全球癌症相关死亡的主要原因。大多数非小细胞肺癌（NSCLC）患者在诊断时已处于疾病晚期，因此5年生存率降至约5%。免疫检查点抑制剂（ICIs）可作用于癌症免疫反应的抑制途径，从而恢复和维持抗肿瘤免疫力。目前已有针对不同途径的ICIs，包括程序性细胞死亡蛋白1（PD-1）、程序性细胞死亡配体1（PD-L1）和细胞毒性T淋巴细胞抗原4（CTLA-4）途径。自2015年3月以来，美国食品药品监督管理局（FDA）批准纳武单抗（抗PD-1抗体）作为晚期鳞状NSCLC患者治疗的二线选择。此外，一系列与PD-1/PD-L1免疫检查点相关的抑制剂有助于NSCLC患者的免疫治疗，并改变了原有的治疗模式。然而，在具有靶向致癌基因突变的亚组中使用ICIs仍存在争议，这是我们需要解决的问题。另一方面，人们不断努力寻找能有效预测ICIs反应的生物标志物，以筛选合适的人群。在本综述中，我们回顾了癌症免疫治疗不断发展的历史，总结了免疫检查点途径的作用机制。最后，基于近期一线试验的结果，我们提出了一种潜在的一线免疫治疗策略，用于治疗NSCLC患者。
