克服肺癌晚期小细胞免疫疗法耐药性：对机制和治疗机会的见解
Overcoming immunotherapy resistance in extensive-stage small cell lung cancer: Insights into mechanisms and therapeutic opportunities.
摘要(中文译文)
广泛期小细胞肺癌（ES-SCLC）是一种高度侵袭性的神经内分泌恶性肿瘤。尽管化学免疫治疗改善了初始预后，但多层面耐药机制的迅速出现严重损害了长期生存，而传统挽救治疗疗效的平台期进一步加剧了这一挑战。随着旨在逆转免疫“冷”表型的策略在转化研究中遭遇障碍，靶向DLL3和B7-H3等表面蛋白的抗体药物偶联物（ADCs）和T细胞衔接器（TCEs）正通过独特的非MHC依赖性细胞毒性重塑治疗格局。本综述阐明了驱动免疫耐药的分子网络，并重点介绍了这些新兴治疗模式的临床突破。最后，我们勾勒了下一代精准肿瘤学的战略路线图，整合生物标志物在治疗中的应用优势、用于分层的动态液体活检、优化的毒性管理以及反向转化的利用。
Abstract
Extensive-stage small-cell lung cancer (ES-SCLC) represents a highly aggressive neuroendocrine malignancy. While chemoimmunotherapy has improved initial prognosis, long-term survival is severely compromised by the rapid emergence of multifaceted resistance mechanisms, a challenge further compounded by the plateaued efficacy of traditional salvage therapies. As strategies aimed at reversing the immunologically "cold" phenotype encounter translational challenges, antibody-drug conjugates (ADCs) and T-cell engagers (TCEs) targeting surface proteins such as DLL3 and B7-H3 are reshaping the therapeutic landscape via unique MHC-independent cytotoxicity. This review elucidates the molecular networks driving immune resistance and highlights clinical breakthroughs in these emerging modalities. Finally, we outline a strategic roadmap for next-generation precision oncology, integrating advantages of biomarkers in treatment, dynamic liquid biopsy for stratification, optimized toxicity management, and the leverage of reverse translation.
如何引用
AMA
Ruonan Guan, Chenyue Zhang, Juntao Zhang, Shanshan Du, Haoyu Wang, Yulin Zhang, et al. Overcoming immunotherapy resistance in extensive-stage small cell lung cancer: Insights into mechanisms and therapeutic opportunities.. Critical reviews in oncology/hematology. 2026; doi:10.1016/j.critrevonc.2026.105411.
APA
Ruonan Guan, Chenyue Zhang, Juntao Zhang, Shanshan Du, Haoyu Wang, Yulin Zhang, et al (2026). Overcoming immunotherapy resistance in extensive-stage small cell lung cancer: Insights into mechanisms and therapeutic opportunities.. Critical reviews in oncology/hematology. https://doi.org/10.1016/j.critrevonc.2026.105411
GB/T 7714
Ruonan Guan, Chenyue Zhang, Juntao Zhang, Shanshan Du, Haoyu Wang, Yulin Zhang, et al. Overcoming immunotherapy resistance in extensive-stage small cell lung cancer: Insights into mechanisms and therapeutic opportunities.[J]. Critical reviews in oncology/hematology, 2026 doi:10.1016/j.critrevonc.2026.105411.
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