免疫检查点抑制剂治疗相关胸腔积液的研究进展

doi:10.19401/j.cnki.1007-3639.2025.03.010

摘要/Abstract

摘要：

肿瘤免疫治疗作为一种新兴的治疗手段，近年来取得了显著进展，已成为继手术、放疗、化疗和靶向治疗之后的重要肿瘤治疗措施。特别是免疫检查点抑制剂（immune checkpoint inhibitors，ICIs）的临床应用，不仅提高了难治性或复发性肿瘤患者的生存率，也极大地优化了肿瘤治疗的整体策略。然而，随着接受免疫治疗的肿瘤患者人群的逐渐扩大，免疫治疗在带来临床获益的同时，也引发了一系列特殊的不良反应，即免疫相关不良反应（immune-related adverse events，irAEs）。在肿瘤患者中，胸腔积液是一种常见且严重的并发症，它对患者的生活质量和治疗效果均有显著影响。通常，肿瘤相关胸腔积液多为胸膜转移，恶性胸腔积液（malignant pleural effusion，MPE）产生迅速、难以控制且易反复。但随着新药物的批准以及现有药物适应证的拓展，接受ICIs治疗的癌症患者数量越来越多，ICIs治疗相关胸腔积液也逐渐引起了重视。ICIs治疗相关胸腔积液在临床上较为罕见，但其与患者的治疗选择和生存预后紧密相关。与MPE不同，ICIs治疗相关胸腔积液的发病机制更为复杂，除了非特异性的免疫激活导致自身免疫性炎症反应的发生外，还可能与胸膜结节病样肉芽肿反应、嗜酸粒细胞性慢性胸膜炎及肿瘤浸润性淋巴细胞相关。在诊断方面，ICIs治疗相关胸腔积液通常采用排除性诊断的方法，诊断过程中需排除肿瘤进展、放疗及化疗等其他肿瘤相关治疗引起的胸腔积液，这无疑增加了诊断的复杂性和难度。ICIs治疗相关胸腔积液的治疗多采用糖皮质激素、他克莫司或英夫利西单抗等药物，通过抑制过强的免疫反应来减轻患者的症状和改善预后。预防ICIs治疗相关胸腔积液的发生同样重要，这要求医师在应用ICIs前对患者进行综合评估，并在治疗期间持续监测，以期在早期发现并处理潜在的不良反应。通过这种综合管理方法，来最大限度地减少ICIs治疗相关胸腔积液对患者生活质量和治疗效果的影响，同时优化患者的整体治疗结果。本综述旨在探讨ICIs治疗相关胸腔积液的发病机制、病理学特征、临床表现、诊断方法及治疗策略等，通过深入分析ICIs治疗相关胸腔积液的特点，以期更好地理解这一并发症，为临床实践提供参考。

关键词: 恶性肿瘤, 免疫检查点抑制剂, 胸腔积液, 不良反应, 治疗

Abstract:

Immunotherapy for cancer, as an emerging treatment modality, has made significant strides in recent years and has become a crucial therapeutic approach following surgery, radiotherapy, chemotherapy, and targeted therapy. In particular, the clinical utilization of immune checkpoint inhibitors (ICIs) has not only enhanced the survival rates of patients with refractory or recurrent tumors but has also significantly optimized the overall strategy for cancer treatment. However, as the population undergoing cancer immunotherapy continues to grow, this expansion not only yields clinical benefits but also precipitates a range of specific adverse reactions known as immune-related adverse events (irAEs). Pleural effusion is a common and severe complication in cancer patients, significantly affecting both their quality of life and treatment outcomes. Typically, tumor-related pleural effusion is often due to pleural metastasis, with malignant pleural effusion (MPE) characterized by rapid growth, being difficult to control, and tendency for recurrence. With the approval of new drugs and the expansion of indications for existing medications, the number of cancer patients receiving ICIs treatment is increasing, bringing ICIs-related pleural effusion into focus. While ICIs treatment-related pleural effusion is relatively rare in clinical practice, it is closely linked to treatment choices of patients and prognosis. Unlike MPE, the pathogenesis of ICIs treatment-related pleural effusion is more complex, not only involving non-specific immune activation leading to autoimmune inflammatory reactions but also potentially related to nodular pleural granulomatous reactions, eosinophilic chronic pleurisy, and tumor-infiltrating lymphocytes. In terms of diagnosis, ICIs treatment-related pleural effusion is typically diagnosed through exclusion, requiring the exclusion of other causes such as tumor progression, radiotherapy, and chemotherapy-induced pleural effusion, adding complexity and difficulty to the diagnostic process. Treatment for ICIs treatment-related pleural effusion often involves glucocorticoids, tocilizumab, or infliximab, aiming to alleviate symptoms and improve prognosis by suppressing excessive immune reactions. Preventing the occurrence of ICIs treatment-related pleural effusion is equally crucial, necessitating comprehensive patient assessment before ICIs administration and continuous monitoring during treatment to promptly detect and manage potential adverse reactions. Through this comprehensive management approach, the impact of ICIs treatment-related pleural effusion on patient quality of life and treatment outcomes can be minimized, optimizing overall treatment results. This review aimed to explore the pathogenesis, histological features, clinical manifestations, diagnostic methods and treatment strategies of ICIs treatment-related pleural effusion, and delve into the characteristics of ICIs treatment-related pleural effusion, in order to enhance understanding of this complication and provide a reference for clinical practice.

Key words: Malignant tumor, Immune checkpoint inhibitors, Pleural effusion, Adverse events, Treatment

中图分类号:

R730.51

安天棋, 田建辉, 周奕阳, 罗斌, 阙祖俊, 刘瑶, 于盼, 赵瑞华, 杨蕴. 免疫检查点抑制剂治疗相关胸腔积液的研究进展[J]. 中国癌症杂志, 2025, 35(3): 333-338.

AN Tianqi, TIAN Jianhui, ZHOU Yiyang, LUO Bin, QUE Zujun, LIU Yao, YU Pan, ZHAO Ruihua, YANG Yun. Research progress on treatment of pleural effusion related to immune checkpoint inhibitors[J]. China Oncology, 2025, 35(3): 333-338.

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