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| 非小细胞肺癌免疫治疗超进展：从机制探索到临床管理的挑战与展望 |
| Application of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Hyperprogressive Disease—Current Status, Mechanisms, and Clinical Management |
| 投稿时间：2026-04-14 修订日期：2026-05-18 |
| DOI： |
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| 中文关键词: 非小细胞肺癌 免疫检查点抑制剂 超进展 肿瘤微环境 生物标志物 临床管控 |
| 英文关键词:Non-small cell lung cancer Immune checkpoint inhibitors Hyperprogressive disease Tumor microenvironment Biomarkers Clinical management |
| 基金项目:中国中医科学院重点实验室培育专项(ZB2025011)；国家重点研发计划（2024YFC3505501）；中国中医科学院“中国中医药联合研究生院”科教专项（CI2025C012LH）。 |
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| 中文摘要: |
| 免疫检查点抑制剂（immune checkpoint inhibitors，ICIs）的运用显著改善了非小细胞肺癌（non-small cell lung cancer，NSCLC）患者的生存预后，但部分患者出现的超进展（hyperprogressive disease，HPD）现象构成了严峻的临床挑战，其表现为在接受免疫治疗后肿瘤加速增殖，导致预后急剧恶化? 本文旨在系统整理此领域的现状与问题，通过梳理定义、诊断指标以及NSCLC患者中发生HPD的高风险特征，进而分析包括肿瘤驱动基因、免疫微环境重塑、宿主免疫状态及治疗相关要素在内的潜在生物学机制? 并且在此基础上概述了当前用于预测和早期识别HPD标志物的研究进展，评估探讨了面向HPD患者的临床管理办法，同时强调了治疗方案的适时调整与个性化预测干预的重要性? 最后，本文对未来研究方向进行了展望，旨在为优化NSCLC患者免疫诊疗策略、规避HPD发生风险提供思路参考? |
| 英文摘要: |
| The application of immune checkpoint inhibitors (ICIs) has significantly improved the survival outcomes of patients with non-small cell lung cancer (NSCLC); however, the emergence of hyperprogressive disease (HPD) in a subset of patients constitutes a serious clinical challenge. HPD is characterized by accelerated tumor proliferation after immunotherapy, leading to a drastic deterioration of prognosis. This thesis aims to systematically review the current status and outstanding issues in this field by examining the definitions, diagnostic criteria, and high-risk features of HPD in NSCLC patients, and further analyze the potential biological mechanisms, including tumor driver genes, immune microenvironment remodeling, host immune status, and treatment-related factors. On this basis, it outlines the current research progress on biomarkers for predicting and early identifying HPD, evaluates and discusses clinical management strategies for patients with HPD, and emphasizes the importance of timely adjustment of treatment regimens and personalized predictive interventions. Finally, this thesis provides an outlook on future research directions, aiming to offer insights for optimizing immunodiagnostic and therapeutic strategies for NSCLC patients and circumventing the risk of HPD occurrence. |
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