文章：

靶向免疫检查点抑制剂治疗非小细胞肺癌：超越PD-1/PD-L1单克隆抗体

Targeting Immune Checkpoint Inhibitors for Non-Small-Cell Lung Cancer: Beyond PD-1/PD-L1 Monoclonal Antibodies

原文发布日期：6 March 2025

DOI: 10.3390/cancers17050906

类型: Article

开放获取: 是

英文摘要：

Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. Immunotherapy targeting the PD-1/PD-L1 axis has revolutionized treatment, providing durable responses in a subset of patients. However, with fewer than 50% of patients achieving significant benefits, there is a critical need to expand therapeutic strategies. This review explores emerging targets in immune checkpoint inhibition beyond PD-1/PD-L1, including CTLA-4, TIGIT, LAG-3, TIM-3, NKG2A, and CD39/CD73. We highlight the biological basis of CD8 T cell exhaustion in shaping the antitumor immune response. Novel therapeutic approaches targeting additional inhibitory receptors (IR) are discussed, with a focus on their distinct mechanisms of action and combinatory potential with existing therapies. Despite significant advancements, challenges remain in overcoming resistance mechanisms and optimizing patient selection. This review underscores the importance of dual checkpoint blockade and innovative bispecific antibody engineering to maximize therapeutic outcomes for NSCLC patients.

摘要翻译： 

非小细胞肺癌（NSCLC）仍是全球癌症相关死亡的主要原因。针对PD-1/PD-L1轴的免疫治疗革新了治疗格局，为部分患者带来持久应答。然而，由于仅不足50%的患者获得显著临床获益，拓展治疗策略具有迫切需求。本综述探讨了超越PD-1/PD-L1的免疫检查点抑制新兴靶点，包括CTLA-4、TIGIT、LAG-3、TIM-3、NKG2A及CD39/CD73。我们重点阐述了CD8 T细胞耗竭在抗肿瘤免疫应答中的生物学基础，讨论了针对其他抑制性受体的新型治疗策略，着重分析其独特作用机制及与现有疗法的联合潜力。尽管取得显著进展，克服耐药机制和优化患者选择仍是当前挑战。本综述强调双检查点阻断策略和创新型双特异性抗体工程技术对最大化NSCLC患者治疗效果的重要意义。

原文链接：

Targeting Immune Checkpoint Inhibitors for Non-Small-Cell Lung Cancer: Beyond PD-1/PD-L1 Monoclonal Antibodies