医学
内科学
肺炎
入射(几何)
HMGB1
肺癌
接收机工作特性
队列
PD-L1
胃肠病学
不利影响
癌症
肿瘤科
肺
免疫疗法
受体
物理
光学
作者
Hiroki Tanahashi,Kakuhiro Yamaguchi,Koji Koyama,Shin-ichi Nakao,Shinjiro Sakamoto,Yasushi Horimasu,Takeshi Masuda,Shintaro Miyamoto,Taku Nakashima,Hiroshi Iwamoto,Kazunori Fujitaka,Hironobu Hamada,Toru Oga,M. Oka,Noboru Hattori
出处
期刊:Respirology
[Wiley]
日期:2022-11-29
卷期号:28 (4): 380-388
摘要
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.
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