Liu Jianhua, Cai Yin, Liu Jiang, Chen Dadong, Wu Xiang
Department of Otorhinolaryngology, Xinghua People's Hospital Affiliated to Yangzhou University, Xinghua, Jiangsu, People's Republic of China.
Department of Oncology, Xinghua People's Hospital Affiliated to Yangzhou University, Xinghua, Jiangsu, People's Republic of China.
Onco Targets Ther. 2025 Aug 29;18:953-966. doi: 10.2147/OTT.S539978. eCollection 2025.
Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer, and high programmed death-ligand 1 (PD-L1) expression (≥50%) is a key biomarker for predicting clinical benefit from immune checkpoint inhibitors (ICIs). This therapy has substantially improved long-term survival rates, with a five-year survival rate exceeding 25%. Nevertheless, primary or acquired resistance occurs in 30-40% of PD-L1-high patients. This resistance arises from multifactorial mechanisms involving tumor-intrinsic adaptations, immune microenvironment reprogramming, and extrinsic immunosuppressive signals. In this review, we systematically dissect the biological and clinical drivers of ICIs resistance in PD-L1-high NSCLC and explore emerging strategies to overcome these barriers, including novel combinatorial approaches and biomarker-guided therapies.
非小细胞肺癌（NSCLC）是肺癌最常见的亚型，高程序性死亡配体1（PD-L1）表达（≥50%）是预测免疫检查点抑制剂（ICI）临床获益的关键生物标志物。这种疗法显著提高了长期生存率，五年生存率超过25%。然而，30-40%的高PD-L1患者会出现原发性或获得性耐药。这种耐药源于多因素机制，包括肿瘤内在适应性、免疫微环境重编程和外在免疫抑制信号。在本综述中，我们系统地剖析了高PD-L1非小细胞肺癌中ICI耐药的生物学和临床驱动因素，并探索克服这些障碍的新策略，包括新型联合方法和生物标志物指导的疗法。
