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. 2025 Sep 8;27(7):1864-1877.
doi: 10.1093/neuonc/noaf095.

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  1 , Raoull Hoogendijk  2   1 , Julie A S Lammers  1 , Jasper van der Lugt  1 , Nelleke Tolboom  3   1 , Esther van Mastrigt  1 , Ella de Boed  1 , Thijs J M van den Broek  1 , Lennart A Kester  1 , Dannis G van Vuurden  1 , Bastiaan B J Tops  1 , Eelco W Hoving  1 , Pieter Wesseling  4   1 , Sabine L A Plasschaert  1
Affiliations

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 et al. Neuro Oncol. .

Abstract

Background: Pediatric 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.

Methods: We 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.

Results: Large 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.

Conclusions: Our 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.

Keywords: B7-H3; antigen-targeting therapy; diffuse midline glioma; pediatric CNS tumor.

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