Immunotherapy Resistance and Therapeutic Strategies in PD-L1 High Expression Non-Small Cell Lung Cancer.

IF 2.8 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

OncoTargets and therapy Pub Date : 2025-08-29 eCollection Date: 2025-01-01 DOI:10.2147/OTT.S539978

Jianhua Liu, Yin Cai, Jiang Liu, Dadong Chen, Xiang Wu

引用次数: 0

Abstract

Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer, and high programmed death-ligand 1 (PD-L1) expression (≥50%) is a key biomarker for predicting clinical benefit from immune checkpoint inhibitors (ICIs). This therapy has substantially improved long-term survival rates, with a five-year survival rate exceeding 25%. Nevertheless, primary or acquired resistance occurs in 30-40% of PD-L1-high patients. This resistance arises from multifactorial mechanisms involving tumor-intrinsic adaptations, immune microenvironment reprogramming, and extrinsic immunosuppressive signals. In this review, we systematically dissect the biological and clinical drivers of ICIs resistance in PD-L1-high NSCLC and explore emerging strategies to overcome these barriers, including novel combinatorial approaches and biomarker-guided therapies.

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PD-L1高表达非小细胞肺癌的免疫耐药及治疗策略

非小细胞肺癌（NSCLC）是肺癌最常见的亚型，程序性死亡配体1 （PD-L1）的高表达（≥50%）是预测免疫检查点抑制剂（ICIs）临床获益的关键生物标志物。这种疗法大大提高了长期生存率，5年生存率超过25%。然而，原发性或获得性耐药发生在30-40%的pd - l1高患者中。这种耐药性来自多因素机制，包括肿瘤内在适应、免疫微环境重编程和外源性免疫抑制信号。在这篇综述中，我们系统地剖析了pd - l1高NSCLC中ICIs耐药的生物学和临床驱动因素，并探索了克服这些障碍的新策略，包括新的组合方法和生物标志物引导疗法。

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

OncoTargets and therapy BIOTECHNOLOGY & APPLIED MICROBIOLOGY-ONCOLOGY

CiteScore

9.70

自引率

0.00%

发文量

221

审稿时长

1 months

期刊介绍： OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer. The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype. Specific topics covered by the journal include: -Novel therapeutic targets and innovative agents -Novel therapeutic regimens for improved benefit and/or decreased side effects -Early stage clinical trials Further considerations when submitting to OncoTargets and Therapy: -Studies containing in vivo animal model data will be considered favorably. -Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines. -Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples. -Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Single nucleotide polymorphism (SNP) studies will not be considered.