Zhou Lu, Uemura Takehiro, Abbar Baptiste, Deng Senyi
Institute of Thoracic Oncology and Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.
Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
Transl Lung Cancer Res. 2025 Aug 31;14(8):3249-3269. doi: 10.21037/tlcr-2025-754. Epub 2025 Aug 18.
With increasing understanding of tumor immune tolerance mechanisms, a series of immune checkpoint molecules have been identified. Immune checkpoint blockade (ICB) therapy, which was developed based on these discoveries, has emerged as a promising strategy for the clinical treatment of non-small cell lung cancer (NSCLC), and has shown notable therapeutic benefits. However, the limited response rate remains a major barrier to further improving ICB efficacy and poses a significant challenge to the clinical management of NSCLC. This review summarizes recent advances in clinical immunotherapy for NSCLC and discusses future prospects in the field.
A systematic literature search was performed using the official websites of organizations and databases, including PubMed, the United States (US) Food and Drug Administration (FDA), China's National Medical Products Administration (NMPA), the National Cancer Institute (NCI), the National Comprehensive Cancer Network (NCCN), the Chinese Society of Clinical Oncology (CSCO), the American Society of Clinical Oncology (ASCO), and the European Society for Medical Oncology (ESMO) The inclusion criteria were: (I) English-language articles published between 2004 and 2025; and (II) clinical studies specifically addressing immune checkpoint inhibitor (ICI) therapy in NSCLC populations.
Researchers have explored various approaches from drug development and treatment response evaluation to combination strategies, and have made substantial progress in enhancing the effectiveness of ICB therapy.
ICB therapy for NSCLC has evolved from monotherapy to multimodal combination approaches, and significant breakthroughs have been achieved; however, three major challenges persist; that is, acquired drug resistance, a lack of reliable biomarkers, and the suboptimal management of special patient populations. To address these issues, future research should focus on: (I) elucidating resistance mechanisms through multi-omics approaches; (II) developing novel biomarkers and next-generation targeted agents; and (III) refining combination therapy regimens. These coordinated efforts will ultimately enable personalized precision immunotherapy tailored to individual patients' molecular profiles and clinical characteristics.
随着对肿瘤免疫耐受机制的认识不断加深，一系列免疫检查点分子已被识别。基于这些发现开发的免疫检查点阻断（ICB）疗法已成为非小细胞肺癌（NSCLC）临床治疗的一种有前景的策略，并已显示出显著的治疗益处。然而，有限的缓解率仍然是进一步提高ICB疗效的主要障碍，对NSCLC的临床管理构成重大挑战。本综述总结了NSCLC临床免疫治疗的最新进展，并讨论了该领域的未来前景。
使用组织和数据库的官方网站进行系统的文献检索，包括PubMed、美国食品药品监督管理局（FDA）、中国国家药品监督管理局（NMPA）、美国国立癌症研究所（NCI）、美国国立综合癌症网络（NCCN）、中国临床肿瘤学会（CSCO）、美国临床肿瘤学会（ASCO）和欧洲医学肿瘤学会（ESMO）。纳入标准为：（I）2004年至2025年发表的英文文章；（II）专门针对NSCLC人群免疫检查点抑制剂（ICI）治疗的临床研究。
研究人员从药物开发、治疗反应评估到联合策略等方面探索了各种方法，并在提高ICB治疗效果方面取得了实质性进展。
NSCLC的ICB治疗已从单药治疗发展到多模式联合治疗方法，并取得了重大突破；然而，三个主要挑战仍然存在，即获得性耐药、缺乏可靠的生物标志物以及特殊患者群体的管理欠佳。为解决这些问题，未来的研究应集中在：（I）通过多组学方法阐明耐药机制；（II）开发新型生物标志物和下一代靶向药物；（III）优化联合治疗方案。这些协同努力最终将实现根据个体患者的分子特征和临床特点量身定制的个性化精准免疫治疗。
