Hu Junjie, Zhang Jing, Wan Shiyue, Zhang Peng
School of Medicine, Tongji University, Shanghai 200092, China.
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China.
Chin Med J Pulm Crit Care Med. 2024 Dec 12;2(4):224-239. doi: 10.1016/j.pccm.2024.11.003. eCollection 2024 Dec.
Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for resectable non-small cell lung cancer. Numerous trials have explored the use of ICIs, either as monotherapy or in combination with other therapies, in the neoadjuvant setting for stage I-III non-small cell lung cancer. Most trials have demonstrated neoadjuvant immunotherapy to be safe and to have remarkable efficacy, with a high pathological response rate and significantly improved event-free survival. This review summarizes the findings of Phase I-III clinical trials investigating various neoadjuvant regimens, including ICI monotherapy, ICI therapy combined with chemotherapy, ICI plus anti-angiogenic therapy, dual ICI therapy, and ICI therapy in combination with radiotherapy or chemoradiotherapy. We discuss the benefits and outcomes associated with each approach. Despite the results being promising, several unresolved issues remain, including identification of reliable biomarkers, the appropriate duration of therapy, the optimal treatment regimen for tumors with high programmed cell death ligand 1 (PD-L1) expression, the false-negative pathological complete response rate, and the role of digital pathology in assessing the response to treatment. Resistance to immunotherapy, in particular, remains a significant barrier to effective use of ICIs. Given the critical influence of the tumor microenvironment (TME) on the response to treatment, we examine the characteristics of the TME in both responsive and resistant tumors as well as the dynamic changes that occur in the TME in response to neoadjuvant immunotherapy. We also summarize the mechanisms underlying T cell responses following neoadjuvant immunotherapy and provide a perspective on strategies to enhance the understanding of tumor heterogeneity, therapy-driven TME remodeling, and overcoming resistance to therapy. Finally, we propose future directions for advancements in personalized neoadjuvant immunotherapy.
免疫检查点抑制剂（ICI）已经改变了可切除非小细胞肺癌的治疗格局。众多试验探索了ICI作为单一疗法或与其他疗法联合，在I - III期非小细胞肺癌新辅助治疗中的应用。大多数试验表明新辅助免疫疗法是安全的，且具有显著疗效，病理缓解率高，无事件生存期显著改善。本综述总结了研究各种新辅助治疗方案的I - III期临床试验结果，包括ICI单一疗法、ICI联合化疗、ICI联合抗血管生成治疗、双ICI疗法以及ICI联合放疗或放化疗。我们讨论了每种方法的益处和结果。尽管结果很有前景，但仍有几个未解决的问题，包括可靠生物标志物的识别、合适的治疗持续时间、高程序性细胞死亡配体1（PD - L1）表达肿瘤的最佳治疗方案、假阴性病理完全缓解率以及数字病理学在评估治疗反应中的作用。特别是对免疫疗法的耐药性仍然是有效使用ICI的重大障碍。鉴于肿瘤微环境（TME）对治疗反应的关键影响，我们研究了反应性和耐药性肿瘤中TME的特征以及TME对新辅助免疫疗法的动态变化。我们还总结了新辅助免疫疗法后T细胞反应的潜在机制，并就增强对肿瘤异质性、治疗驱动的TME重塑以及克服治疗耐药性的理解的策略提供了观点。最后，我们提出了个性化新辅助免疫疗法未来的发展方向。
