ArticlePediatric blood & cancer2018
Specific expression of PD-L1 in RELA-fusion supratentorial ependymoma: Implications for PD-1-targeted therapy.
Article in Pediatric blood & cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 70 citations in OpenAlex.
- Nivolumab with or without ipilimumab in pediatric patients with high-grade CNS malignancies: Safety, efficacy, biomarker, and pharmacokinetics-CheckMate 908.Neuro-oncology · 2023Trial
- The role of clinical factors and immunocheckpoint molecules in the prognosis of patients with supratentorial extraventricular ependymoma: a single-center retrospective study.Journal of cancer research and clinical oncology · 2021Trial
- Newly Diagnosed Metastatic Intracranial Ependymoma in Children: Frequency, Molecular Characteristics, Treatment, and Outcome in the Prospective HIT Series.The oncologist · 2019Trial
- Chromosome 6q mediated loss of LATS1 tumour suppression as a targetable mechanism of ultra-high-risk posterior fossa A ependymoma.Acta neuropathologica · 2026Article
- Ultrasound-Enhanced Drug Delivery in Pediatric Neuro-Oncology: A New Therapeutic Strategy.Pharmaceutics · 2026Review
- Article
- Evaluating temozolomide for pediatric adamantinomatous craniopharyngiomas using microspheroid-based drug screening.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026Article
- Overcoming immunotherapy barriers in pediatric brain tumors: epigenetic strategies.Frontiers in oncology · 2026Review
- Algorithm-based assessment of T-cell dysfunction and exclusion to forecast ICB sensitivity in pediatric brain ependymoma.Journal of neuro-oncology · 2025Article
- Recurrent adamantinomatous craniopharyngiomas show MAPK pathway activation, clonal evolution and rare TP53-loss-mediated malignant progression.Acta neuropathologica communications · 2024Article
- Pediatric Solid Cancers: Dissecting the Tumor Microenvironment to Improve the Results of Clinical Immunotherapy.International journal of molecular sciences · 2024Review
- Multi-omic approach identifies hypoxic tumor-associated myeloid cells that drive immunobiology of high-risk pediatric ependymoma.iScience · 2023Article
- Characterizing the tumor immune microenvironment of ependymomas using targeted gene expression profiles and RNA sequencing.Cancer immunology, immunotherapy : CII · 2023Article
- Immunobiology and Cytokine Modulation of the Pediatric Brain Tumor Microenvironment: A Scoping Review.Cancers · 2023Article
- A clinicopathological analysis of supratentorial ependymoma, ZFTA fusion-positive: utility of immunohistochemical detection of CDKN2A alterations and characteristics of the immune microenvironment.Brain tumor pathology · 2023Article
- The Role of Immunotherapy in the Treatment of Rare Central Nervous System Tumors.Current oncology (Toronto, Ont.) · 2023Review
- Role of regulation of PD-1 and PD-L1 expression in sepsis.Frontiers in immunology · 2023Review
- Spinal ependymoma in adults: from molecular advances to new treatment perspectives.Frontiers in oncology · 2023Review
- The biology of ependymomas and emerging novel therapies.Nature reviews. Cancer · 2022Review
- Current Advances in the Management of Adult Craniopharyngiomas.Current oncology (Toronto, Ont.) · 2022Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundA desperate need for novel therapies in pediatric ependymoma (EPN) exists, as chemotherapy remains ineffective and radiotherapy often fails. EPN have significant infiltration of immune cells, which correlates with outcome. Immune checkpoint inhibitors provide an avenue for new treatments. This study characterizes tumor-infiltrating immune cells in EPN and aims at predicting candidates for clinical trials using checkpoint inhibitors targeting PD-L1/PD-1 (programmed death ligand 1/programmed death 1).
methodsThe transcriptomic profiles of the primary study cohort of EPN and other pediatric brain tumors were interrogated to identify PD-L1 expression levels. Transcriptomic findings were validated using the western blotting, immunohistochemistry and flow cytometry.
resultsWe evaluated PD-L1 mRNA expression across four intracranial subtypes of EPN in two independent cohorts and found supratentorial RELA fusion (ST-RELA) tumors to have significantly higher levels. There was a correlation between high gene expression and protein PD-L1 levels in ST-RELA tumors by both the western blot and immunohistochemisty. The investigation of EPN cell populations revealed PD-L1 was expressed on both tumor and myeloid cells in ST-RELA. Other subtypes had little PD-L1 in either tumor or myeloid cell compartments. Lastly, we measured PD-1 levels on tumor-infiltrating T cells and found ST-RELA tumors express PD-1 in both CD4 and CD8 T cells. A functional T-cell exhaustion assay found ST-RELA T cells to be exhausted and unable to secrete IFNγ on stimulation.
conclusionsThese findings in ST-RELA suggest tumor evasion and immunsuppression due to PD-L1/PD-1-mediated T-cell exhaustion. Trials of checkpoint inhibitors in EPN should be enriched for ST-RELA tumors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.