Addressing clinical needs in NSCLC immunotherapy: Mechanisms of resistance and promising combination strategies.

IF 10.6 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-09-16 Epub Date: 2025-08-27 DOI:10.1016/j.xcrm.2025.102315

Kai Kang, Shanghai Liu, Zhuoran Yao, Jianxin Xue, You Lu

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引用次数: 0

Abstract

PD-(L)1 monoclonal antibody-based immunotherapy has become the cornerstone of treatment for non-small cell lung cancer without driver gene alterations. However, resistance, including primary and acquired resistance, remains a major clinical challenge. In this review, we summarize the delayed separation of progression-free survival curves observed in randomized clinical trials, which reflects the emergence of resistance at different treatment stages and the dynamic evolution of anti-tumor immune responses. The development of effective combination strategies should therefore be guided by a thorough understanding of the complex biological mechanisms governing tumor-immune interactions. We review the underlying mechanisms of immunotherapy resistance and propose potential combination strategies. Finally, we emphasize several key considerations for future clinical trial design, including the sequencing of combination therapies, biomarker-guided treatment selection, and optimized management of treatment-related toxicities.

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解决非小细胞肺癌免疫治疗的临床需求：耐药机制和有希望的联合策略。

PD-(L)1单克隆抗体为基础的免疫疗法已成为治疗无驱动基因改变的非小细胞肺癌的基石。然而，耐药性，包括原发性和获得性耐药性，仍然是一个主要的临床挑战。在这篇综述中，我们总结了随机临床试验中观察到的无进展生存曲线的延迟分离，这反映了不同治疗阶段耐药的出现和抗肿瘤免疫反应的动态演变。因此，有效联合策略的发展应以对控制肿瘤-免疫相互作用的复杂生物学机制的透彻理解为指导。我们回顾了免疫治疗耐药的潜在机制，并提出了潜在的联合策略。最后，我们强调了未来临床试验设计的几个关键考虑因素，包括联合治疗的测序，生物标志物引导的治疗选择，以及治疗相关毒性的优化管理。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.