Kang Li-Ping, Huang Hua-Jing, Xu Cong, Chen Hui-Hui, Huang Dong-Hui, Jiang Ze-Bo
Zhuhai Hospital of Integrated Traditional Chinese & Western Medicine, Zhuhai, Guangdong, China.
Northeastern University, Boston, MA, United States.
Front Immunol. 2025 Sep 2;16:1630940. doi: 10.3389/fimmu.2025.1630940. eCollection 2025.
Immune checkpoint therapy has emerged as a revolutionary approach in the field of non-small cell lung cancer (NSCLC), offering new hope to patients with various malignancies. Despite its success, a significant proportion of patients exhibit primary or acquired resistance, limiting the efficacy of these treatments. This review provides a comprehensive analysis of recent breakthroughs in immune checkpoint therapy, focusing on the underlying biology of immune checkpoints, current checkpoint inhibitors, and the mechanisms of resistance that challenge treatment effectiveness. In particular, we will explore novel strategies designed to overcome these resistance mechanisms, including combination therapies that enhance anti-tumor immune responses, the use of personalized neoantigen vaccines, and microbiome-modulating therapies. Additionally, we will examine the role of emerging biomarkers, such as TCR clonality and T-cell inflamed gene signatures, in predicting patient responses. By synthesizing these insights, this review aims to highlight innovative approaches that could significantly improve therapeutic outcomes for patients with NSCLC and other malignancies, ultimately advancing the field of cancer immunotherapy.
免疫检查点疗法已成为非小细胞肺癌（NSCLC）领域的一种革命性方法，为患有各种恶性肿瘤的患者带来了新希望。尽管取得了成功，但仍有相当一部分患者表现出原发性或获得性耐药，限制了这些治疗方法的疗效。本综述对免疫检查点疗法的最新突破进行了全面分析，重点关注免疫检查点的基础生物学、当前的检查点抑制剂以及挑战治疗效果的耐药机制。特别是，我们将探索旨在克服这些耐药机制的新策略，包括增强抗肿瘤免疫反应的联合疗法、个性化新抗原疫苗的使用以及微生物群调节疗法。此外，我们将研究新兴生物标志物，如TCR克隆性和T细胞炎症基因特征，在预测患者反应中的作用。通过综合这些见解，本综述旨在突出那些能够显著改善NSCLC和其他恶性肿瘤患者治疗结果的创新方法，最终推动癌症免疫治疗领域的发展。
