ArticleJournal for immunotherapy of cancer2023
Cross-cohort analysis identified an immune checkpoint-based signature to predict the clinical outcomes of neuroblastoma.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.
- Prognostic Significance of B7H3 Expression in Solid Tumors: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2025Pooled it
- Integration of Bulk RNA Sequencing and Single-Cell Sequencing to Identify Prognostic Genes Associated With MCDRGs in Neuroblastoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The B7-H3/CD3 immune phenotype identifies prognostic subgroups in neuroblastoma.Frontiers in immunology · 2026Article
- An immune checkpoint-based score is a prognostic marker in retrospective cohort study of patients with gastric cancer.Translational cancer research · 2025Article
- Targeting TRIM59 impairs RNA splicing and promotes neuroblastoma differentiation and therapeutic responses.Journal of experimental & clinical cancer research : CR · 2025Article
- Emerging clinical and research approaches in targeted therapies for high-risk neuroblastoma.Frontiers in oncology · 2025Review
- CD20Heliyon · 2024Article
- Narrative review: precision medicine applications in neuroblastoma-current status and future prospects.Translational pediatrics · 2024Review
- Identification of novel markers for neuroblastoma immunoclustering using machine learning.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeuroblastoma (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.
methodsImmunohistochemistry 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).
resultsSeven 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 confirmed in the validation set (p<0.001). Multivariate Cox regression analysis demonstrated that age and the ICS were independent risk factors for OS in the discovery set (HR 6.17, 95% CI 1.78 to 21.29 and HR 1.18, 95% CI 1.12 to 1.25, respectively). Furthermore, nomogram A combining the ICS and age demonstrated significantly better prognostic value than age alone in predicting the patients' 1-year, 3-year and 5-year OS in the discovery set (1 year: AUC, 0.891 (95% CI 0.797 to 0.985) vs 0.675 (95% CI 0.592 to 0.758); 3 years: 0.875 (95% CI 0.817 to 0.933) vs 0.701 (95% CI 0.645 to 0.758); 5 years: 0.898 (95% CI 0.851 to 0.940) vs 0.724 (95% CI 0.673 to 0.775), respectively), which was confirmed in the validation set.
conclusionsWe propose an ICS that significantly differentiates between low-risk and high-risk patients, which might add prognostic value to age and provide clues for immunotherapy in NB.
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