抗PD-1/PD-L1免疫检查点抑制剂与肺癌患者2型气道炎症之间的关联：IMMUNEO回顾性病例系列研究
Association Between anti-PD-1/PD-L1 Immune Checkpoint Inhibitors and Type 2 Airway Inflammation in Patients with Lung Cancer: the IMMUNEO Retrospective Case Series.
文献信息
| PMID | 42785630 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Zakaria Lahmar |
| 作者单位 | Department of Respiratory Diseases; Univ Montpellier, CHU Montpellier, Montpellier, France; PhyMedExp, Univ Montpellier, CNRS, INSERM U1046, CHU Montpellier, Montpellier, France. Electronic address: m-lahmar@chu-montpellier.fr. |
| 期刊 | The journal of allergy and clinical immunology. In practice |
| SCI 分区 | Q1 |
| IF | 7.7 |
| 研究类型 | 临床研究 · 临床 |
| 所属专科 | 鼻科 |
中文摘要
背景： 靶向PD-1/PD-L1的免疫检查点抑制剂（ICIs）已彻底改变肺癌治疗，但免疫介导的并发症日益受到关注，其对2型炎症和慢性气道疾病的影响仍不明确。皮质类固醇是嗜酸性气道疾病的标准治疗，但在抗PD-1/PD-L1治疗的患者中却有害。
目的： 我们在真实世界队列中研究了ICIs对血嗜酸性粒细胞计数（BEC）、慢性气道疾病发生和急性加重的影响。
方法： 这项回顾性研究分析了127例连续接受PD-1/PD-L1抑制剂治疗的非小细胞肺癌患者的临床、生物学和影像学数据。收集了BEC、肺功能、合并哮喘或COPD、急性加重频率、皮质类固醇使用情况。ROC曲线确定了预测急性加重风险的嗜酸性粒细胞阈值。
结果： 一半患者患有COPD（n=47）或哮喘（n=13），三分之一为新诊断，11例（8.7%）在治疗期间出现急性加重，其中9例频繁加重（≥2次/年）。BEC在ICI治疗期间显著升高，在急性加重者中升高更明显（p=0.0013）。治疗前BEC >275个细胞/mm3与急性加重发生相关，而治疗期间值 >345个细胞/mm3提供了更好的预测（AUC 0.73，67%敏感性；83%特异性）。在多变量分析中，急性加重与FEV1增加10%呈负相关（OR=0.70；95%CI=0.46-0.99），与 concomitant 全身性皮质类固醇使用呈正相关（OR=10.34；95%CI=1.81-69.27），以及与治疗期间嗜酸性粒细胞升高呈正相关（每102个细胞/mm3，OR=1.15；95%CI=1.01-1.36）。
结论： ICIs可能揭示或放大潜在的T2气道炎症。嗜酸性粒细胞计数升高是一个特异性但预测性较弱的信号，应促使进行监测而非过度解读，而计数低则令人安心。
英文摘要
BACKGROUND: Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have revolutionized lung cancer therapy, but immune-mediated complications are a growing concern, and their impact on type 2 inflammation and chronic airway disease remains unclear. Corticosteroids, standard for eosinophilic airway diseases, are detrimental in anti-PD-1/PD-L1-treated patients.
OBJECTIVE: We investigated the effect of ICIs on blood eosinophil counts (BEC), chronic airway disease development and exacerbations in a real-world cohort.
METHODS: This retrospective study analyzed clinical, biological, and imaging data from 127 consecutive patients treated with PD-1/PD-L1 inhibitors for non-small cell lung cancer. BEC, lung function, comorbid asthma or COPD, frequency of exacerbations, corticosteroid use werecollected. ROC curves identified eosinophil thresholds predictive of exacerbation risk.
RESULTS: Half of the patients had COPD (n=47) or asthma (n=13), one third newly diagnosed, and 11 (8.7%) exacerbated on treatment, 9 of them frequently (≥2/year). BEC increased significantly during ICI, more so among exacerbators (p=0.0013). Pre-treatment BEC >275 cells/mm3 was associated with exacerbation onset, while on-treatment values >345 cells/mm3 offered better prediction (AUC 0.73, 67% sensitivity; 83% specificity). In multivariable analysis, exacerbations were negatively associated with 10% increase in FEV1 (OR=0.70; 95%CI=0.46-0.99) and positively associated with concomitant systemic corticosteroid use (OR=10.34; 95%CI=1.81-69.27), and on-treatment eosinophil rise (OR=1.15; 95%CI=1.01-1.36 per 102 cells/mm3).
CONCLUSION: ICIs may unmask or amplify underlying T2 airway inflammation. A raised eosinophil count is a specific but weakly predictive signal that should prompt surveillance rather than be over-interpreted, whereas a low count is reassuring.