Evidence map›Paper›PMID 40207575›Full record

ArticleNeuro-oncology2025

Do we need B7-H3 immunohistochemistry for the inclusion of children with high-grade central nervous system tumors in clinical trials targeting B7-H3?

Mariëtte E G Kranendonk, Raoull Hoogendijk, Julie A S Lammers, Jasper van der Lugt, Nelleke Tolboom, Esther van Mastrigt, Ella de Boed, Thijs J M van den Broek, Lennart A Kester, Dannis G van Vuurden and 4 more

Abstract read
In one paragraph

Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Review
  6. Review
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Mariëtte E G KranendonkPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.ORCID 0000-0001-9683-7494
Raoull HoogendijkDepartment of Neurology, Brain Tumor Center, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands.
Julie A S LammersPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Jasper van der LugtPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Nelleke TolboomDepartment of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands.
Esther van MastrigtPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Ella de BoedPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Thijs J M van den BroekPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Lennart A KesterPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Dannis G van VuurdenPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Bastiaan B J TopsPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.ORCID 0000-0002-1699-8210
Eelco W HovingPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Pieter WesselingDepartment of Pathology, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, The Netherlands.
Sabine L A PlasschaertPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.

Funding

internal funding sources of the Princess Máxima Center
6 · The paper itself

Abstract

backgroundPediatric high-grade central nervous system (pHG-CNS) tumors are the leading cause of childhood cancer-related deaths, partly due to poor response to standard treatments. B7-H3 is reportedly expressed in pHG-CNS tumors, making antigen-targeting therapies, including anti-B7-H3 chimeric antigen receptor T-cell (CAR-T) therapy, promising. However, given substantial inter-tumoral protein expression diversity in CNS tumors, it's unclear which patients might benefit from these treatments. Therefore, we studied B7-H3 expression in a large set of pHG-CNS tumors.

methodsWe retrospectively analyzed 136 pHG-CNS tumors (embryonal tumors (n = 44), high-grade neuroepithelial tumors (n = 4), ependymomas (n = 30),high-grade gliomas (HGGs, n = 58)) from the Princess Máxima Center for Pediatric Oncology. CD276 mRNA (encoding B7-H3) and immunohistochemical (IHC) protein expression of B7-H3 was measured and correlated to clinical-molecular data.

resultsLarge variability of B7-H3 mRNA and protein expression was observed both between and within tumor types. Many tumors expressed B7-H3, but 30% of diffuse midline glioma H3K27-altered and ependymomas posterior fossa type A showed no or minimal expression. This variability was unrelated to patient age, tumor location, epigenetic subclass, or molecular tumor driver. B7-H3 negative cases were high in tumor cells, ruling out low tumor cell percentage as an explanation for negative staining.

conclusionsOur study of B7-H3-expression in the largest pHG-CNS tumor set to date revealed significant interpatient variability and numerous negative cases. Our results urge for tumor tissue acquisition at enrollment in B7-H3 targeting therapeutic trials (including CAR-T cells) in order to thoroughly assess the value of IHC B7-H3 expression as biomarker and, ultimately, to allow for more tailored therapy.

Indexed as

B7 AntigensBiomarkers, TumorCentral Nervous System NeoplasmsAdolescentChildChild, PreschoolClinical Trials as TopicFemaleFollow-Up StudiesHumansImmunohistochemistryInfantMaleNeoplasm GradingPrognosisRetrospective StudiesB7 AntigensBiomarkers, TumorCD276 protein, humanantigen-targeting therapyB7-H3diffuse midline gliomapediatric CNS tumor

Identifiers

PMID40207575
PMCPMC12417824

What OpenQuestion holds

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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.