A potential mechanism of the onset of acute eosinophilic pneumonia triggered by an anti-PD-1 immune checkpoint antibody in a lung cancer patient
A potential mechanism of the onset of acute eosinophilic pneumonia triggered by an anti-PD-1 immune checkpoint antibody in a lung cancer patient
复制标题
DOI：
10.1002/iid3.238
复制
发表时间：
2019-03-01
影响因子：
3.2
通讯作者：
Tomita, Yusuke
中科院分区：
文献类型：
--
作者：
Jodai, Takayuki;Yoshida, Chieko;Tomita, Yusuke
前言由于免疫网络的复杂性，免疫检查点阻断对癌症患者免疫功能的影响尚未完全阐明。最近的研究表明，程序性细胞死亡配体2(PD-L2)在负向控制CD4+T辅助细胞2型(Th2)细胞因子的产生和气道超敏反应方面具有重要作用，提示PD-1阻断治疗可以使肺内通过PD-1/PD-L2抑制通路的低反应性Th2细胞重新苏醒。方法报道1例晚期非小细胞肺癌患者由抗PD-1抗体nivolumab诱发的急性嗜酸性肺炎(AEP)，称为Th2相关性肺部疾病。基于目前的病例报告和文献，本研究提出了AEP作为一种免疫相关不良事件(IRAE)发病的潜在机制。结果1例62岁男性患者确诊为肺腺癌，三线方案为尼伏单抗。经过三个周期的nivolumab治疗后，胸部计算机断层扫描显示两个肺都有肺浸润性病变。患者根据AEP的诊断标准诊断为AEP。停用尼伏卢单抗，患者开始口服强的松龙。他的症状和放射学结果迅速改善。结论随着抗PD-1抗体使用频率的增加，临床医生应该意识到AEP作为一种潜在的IRAE的风险。这项研究可能会提高我们对Th2相关irAEs和AEP背后的病理生理学的理解。
Introduction The impact of immune checkpoint blockade on immunity in cancer patients is not completely elucidated due to the complexity of the immune network. Recent studies have revealed a significant role of programed cell death-ligand 2 (PD-L2) in negatively controlling the production of CD4+ T helper type 2 (Th2) cytokines and airway hypersensitiveness, suggesting hypo-responsive Th2 cells via the PD-1/PD-L2 inhibitory pathway in lung could be reawaken by PD-1 blockade therapy. Methods We describe the first report of acute eosinophilic pneumonia (AEP), which is known as Th2-associated pulmonary disease, triggered by nivolumab, an anti-PD-1 antibody, in an advanced non-small cell lung cancer patient. Based on the current case report and literature, the present study proposes a potential mechanism of the onset of AEP as an immune-related adverse event (irAE). Results A 62-year-old man was diagnosed with lung adenocarcinoma and nivolumab was selected as the third-line regimen. After three cycles of nivolumab treatment, chest computed tomography revealed pulmonary infiltrates in both lungs. The patient was diagnosed with AEP based on the diagnostic criteria for AEP. Nivolumab was suspended and the patient was started on oral prednisolone. His symptoms and radiological findings had rapidly improved. Conclusions Given the increasing frequency of the use of anti-PD-1 antibodies, clinicians should be aware of the risk of AEP as a potential irAE. This study may improve our understanding of the pathophysiology underlying Th2-associated irAEs and AEP.