| 郭小僮,邓立力.晚期非小细胞肺癌一线免疫治疗耐药机制及其对策的研究进展[J].肿瘤学杂志,2026,32(3):185-191. |
| 晚期非小细胞肺癌一线免疫治疗耐药机制及其对策的研究进展 |
| Mechanisms and Therapeutic Strategies for Resistance to First-Line Immunotherapy in Advanced Non-Small Cell Lung Cancer |
| 投稿时间：2025-08-06 |
| DOI：10.11735/j.issn.1671-170X.2026.03.B002 |
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| 中文关键词: 非小细胞肺癌 免疫治疗 耐药 二线治疗 |
| 英文关键词:non-small cell lung cancer immunotherapy drug resistance second-line therapy |
| 基金项目:吴阶平医学基金会临床科研专项资助基金（320.6750. 2023-17-10；320.6750.2022-18-36） |
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| 中文摘要: |
| 摘 要：免疫治疗是晚期非小细胞肺癌（non-small cell lung cancer，NSCLC）一线治疗的重要手段。而大多数患者都会面临耐药，耐药并非单一事件，而是肿瘤在免疫压力下动态演化的结果，其核心机制涵盖肿瘤细胞的免疫原性下调和肿瘤微环境的免疫抑制性重塑。针对一线免疫耐药后的二线治疗方案存在争议，目前临床上主要考虑患者的具体病情、体力状况、程序性死亡配体1表达情况、驱动基因突变状态以及前期治疗反应等因素来制定个性化治疗策略。二线化疗、靶向治疗、免疫再挑战都是可选的策略，也有双免疫、抗体药物偶联物等新药的应用。本综述主要介绍晚期NSCLC一线免疫耐药后二线不同的治疗方案。 |
| 英文摘要: |
| Abstract： Immunotherapy has become a cornerstone of first-line treatment for advanced non-small cell lung cancer (NSCLC). However， the majority of patients eventually develop resistance， which arises not as an isolated event but through the dynamic evolution of tumors under immune pressure. Key mechanisms involve diminished immunogenicity of tumor cells and an immunosuppressive tumor microenvironment. The optimal second-line strategy following first-line immunotherapy failure remains controversial. Current clinical decision-making integrates multiple factors， including patient performance status， programmed death-ligand 1 expression， driver mutation profile， and prior treatment response， to tailor personalized therapeutic approaches. Available options encompass chemotherapy， targeted therapy， immunotherapy rechallenge， as well as emerging modalities such as dual immune checkpoint inhibition and antibody-drug conjugates. This review summarizes current evidence and discusses the various second-line treatment strategies for advanced NSCLC after progression on first-line immunotherapy. |
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