抗程序性细胞死亡-1（PD-1）/程序性细胞死亡配体-1（PD-L1）抗体引起的检查点抑制剂肺炎（CIP）可能是癌症患者的致命不良事件。但是，目前还没有被识别出CIP的预测性生物标志物。因为高迁移率族群盒子1（HMGB1）可能加重肺部损伤并潜在地增加免疫反应，所以它被作为预测性血液标记进行了调查。在2015年12月至2020年10月之间，我们收集了两家大学医院的87名和43名非小细胞肺癌（NSCLC）患者（分别为发现和验证队列）单次使用抗PD-1/PD-L1治疗前的血样。我们回顾性评估了血清HMGB1水平与在开展抗PD-1/PD-L1治疗后3个月内出现的CIP的发生率之间的关系。在发现和验证队列中，CIP分别发生在9例（10.3％）和6例（14.0％）患者中。在每个队列中，CIP患者的血清HMGB1水平明显且可重复地高于非CIP患者。在发现队列中，通过接收操作特征分析识别出HMGB1阈值为11.24 ng/ml。在发现和验证队列中，HMGB1高亚组的CIP发生率显著高于HMGB1低亚组的CIP发生率（分别为41.2％vs.2.9％和36.4％vs.6.3％）。在探索性大样本分析中，有3名患者死于5级CIP；通过19.29 ng/ml HMGB1阈值将5级CIP检测的灵敏度为100％，特异性为96.85％。我们的结果表明，在NSCLC患者中，HMGB1可能是预测CIP发展和严重程度的潜在血液标记物。 © 2022亚太呼吸学会。

Checkpoint inhibitor pneumonitis (CIP), caused by the anti-programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) antibody, can be a fatal adverse event in cancer patients. However, no predictive biomarkers for CIP have been identified. Because high-mobility group box 1 (HMGB1) can aggravate lung injury and potentially increase the immune response, it was investigated as a predictive blood marker.Blood samples, prospectively stored before anti-PD-1/PD-L1 monotherapy between December 2015 and October 2020, were obtained at two university hospitals from 87 and 43 non-small cell lung cancer (NSCLC) patients (discovery and validation cohorts, respectively). We retrospectively evaluated the association of serum HMGB1 levels with the incidence of CIP developed within 3 months of initiating anti-PD-1/PD-L1 therapy.CIP was observed in 9 (10.3%) and 6 (14.0%) patients in the discovery and validation cohorts, respectively. In each cohort, serum HMGB1 levels were significantly and reproducibly higher in patients with CIP. In the discovery cohort, an HMGB1 cut-off level of 11.24 ng/ml was identified by receiver operating characteristic analysis. CIP incidence in the HMGB1high subgroup was significantly higher than that in the HMGB1low subgroup in the discovery (41.2% vs. 2.9%) and validation cohorts (36.4% vs. 6.3%). In an exploratory pooled analysis, three patients died of grade 5 CIP; a 19.29 ng/ml HMGB1 cut-off level detected grade 5 CIP with 100% sensitivity and 96.85% specificity.Our results suggest that HMGB1 may be a potential blood marker to predict the development and severity of CIP in NSCLC patients.© 2022 Asian Pacific Society of Respirology.