免疫检查点抑制剂相关的间质性肺病（ICI-ILD）是非小细胞肺癌（NSCLC）患者常见的严重不良事件。我们研究了接受ICI治疗的NSCLC患者ICI-ILD的临床效果和作用机制。我们回顾性筛选了接受PD-1/PD-L1单药治疗的晚期或复发NSCLC患者，并检查了ICI-ILD的预后影响。此外，我们分析了治疗前血浆中72种不同可溶性免疫介质的水平，以探索与ICI-ILD发展相关的可能机制。此外，我们还分析了与ICI-ILD发展相关的可溶性免疫介质与生存之间的关系。在141名NSCLC患者中，25名（17.7%）发展出ICI-ILD。逻辑回归分析显示，治疗前的CXCL9、MMP-1、IL-6和IL-19水平与ICI-ILD的发展相关。ICI-ILD患者与非ICI-ILD患者之间在无进展生存期（PFS）和总生存期（OS）方面没有显著差异。在ICI-ILD患者中，较低级别的ICI-ILD患者的总生存期比较高级别的ICI-ILD患者更好。在ICI-ILD患者中，较低级别的ICI-ILD患者的PFS和OS较高级别的ICI-ILD患者更好。在与ICI-ILD相关的四种可溶性免疫介质中，较高水平的IL-19与较差的OS和PFS显著相关。确定的可溶性免疫介质，包括CXCL9、MMP-1、IL-6和IL-19，可能作为与ICI-ILD发展相关的生物标记物。尽管我们未检测到CCI-ILD患者和非ICI-ILD患者之间的PFS和OS的显著差异，但较低级别的ICI-ILD患者的PFS和OS较高级别的ICI-ILD患者更长。在生物标志物中，IL-19可能是ICI-ILD的原因和预后因素。 版权所有© 2023 Elsevier B.V. 保留所有权利。

Immune checkpoint inhibitor-related interstitial lung disease (ICI-ILD) is a serious adverse event frequently observed in patients with non-small cell lung cancer (NSCLC). We investigated the clinical effects and mechanism of action of ICI-ILD in NSCLC patients treated with ICI.We retrospectively screened patients with advanced or recurrent NSCLC who received PD-1/PD-L1 inhibitor monotherapy and examined the prognostic impact of ICI-ILD. In addition, we analyzed the levels of 72 different soluble immune mediators in pre-treatment plasma to explore possible mechanisms associated with the development of ICI-ILD. Furthermore, the relationships between soluble immune mediators associated with ICI-ILD development and survival were analyzed.Of 141 patients with NSCLC, 25 (17.7%) developed ICI-ILD. Logistic regression analysis revealed that pre-treatment CXCL9, MMP-1, IL-6, and IL-19 levels were associated with ICI-ILD development. There were no significant differences in progression-free survival (PFS) and overall survival (OS) between patients with or without ICI-ILD. In patients with ICI-ILD, patients with lower grade ICI-ILD had better OS than those with higher-grade ICI-ILD. In ICI-ILD patients, there was a trend for patients with lower-grade ICI-ILD to have better PFS and OS than those with higher-grade ICI-ILD. Among four soluble immune mediators associated with ICI-ILD, a high level of IL-19 was significantly correlated with worse OS and PFS.The identified soluble immune mediators, including CXCL9, MMP-1, IL-6, and IL-19, may be useful as biomarkers to associate with ICI-ILD development. Although we did not detect significant differences in PFS and OS between patients with and without ICI-ILD, PFS and OS were longer in those with lower-grade ICI-ILD than in patients with higher-grade ICI-ILD. Among biomarkers, IL-19 may be a causal and prognostic factor for ICI-ILD.Copyright © 2023 Elsevier B.V. All rights reserved.