Cross-cohort analysis identified an immune checkpoint-based signature to predict the clinical outcomes of neuroblastoma

作者：Liang Zeng, Hui Xu, Shuhua Li, Shuoyu Xu, Kai Chen, Liang-Jun Qin, Lei Miao, Fang Wang, Ling Deng, Feng‐Hua Wang, Le Li, Sha Fu, Na Liu, Ran Wang, Ying-Qing Li, Haiyun Wang · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2023 · DOI：10.1136/jitc-2022-005980 · 被引用次数：10 · 研究领域：Neuroblastoma Research and Treatments、Cancer Immunotherapy and Biomarkers、Immune cells in cancer

BACKGROUND: Neuroblastoma (NB) places a substantial health burden on families worldwide. This study aimed to develop an immune checkpoint-based signature (ICS) based on the expression of immune checkpoints to better assess patient survival risk and potentially guide patient selection for immunotherapy of NB. METHODS: Immunohistochemistry integrated with digital pathology was used to determine the expression levels of 9 immune checkpoints in 212 tumor tissues used as the discovery set. The GSE85047 dataset (n=272) was used as a validation set in this study. In the discovery set, the ICS was constructed using a random forest algorithm and confirmed in the validation set to predict overall survival (OS) and event-free survival (EFS). Kaplan-Meier curves with a log-rank test were drawn to compare the survival differences. A receiver operating characteristic (ROC) curve was applied to calculate the area under the curve (AUC). RESULTS: Seven immune checkpoints, including PD-L1, B7-H3, IDO1, VISTA, T-cell immunoglobulin and mucin domain containing-3 (TIM-3), inducible costimulatory molecule (ICOS) and costimulatory molecule 40 (OX40), were identified as abnormally expressed in NB in the discovery set. OX40, B7-H3, ICOS and TIM-3 were eventually selected for the ICS model in the discovery set, and 89 patients with high risk had an inferior OS (HR 15.91, 95% CI 8.87 to 28.55, p<0.001) and EFS (HR 4.30, 95% CI 2.80 to 6.62, p<0.001). Furthermore, the prognostic value of the ICS was con...