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Updated: May 16, 2026
A Protocol for Rapid Post-mortem Cell Culture of Diffuse Intrinsic Pontine Glioma (DIPG)
Published on: March 7, 2017
B7-H3, a potential therapeutic target, is expressed in diffuse intrinsic pontine glioma
Zhiping Zhou1, Neal Luther, George M Ibrahim
1Department of Neurological Surgery, Weill Medical College of Cornell University, 1300 York Ave, Box 99, New York, NY 10065, USA. zhz2004@med.cornell.edu
Abstract:
Diffuse intrinsic pontine glioma (DIPG) is a brain cancer with a median survival of only 1 year. Lack of molecular characterization of this tumor impedes the development of novel therapies. Membrane protein B7-H3, aka CD276, involved in interactions with host defenses in certain cancers, has been shown to be over-expressed in the majority of malignant neuroectodermal tumors including adult high-grade glioma. Targeting B7-H3 with a monoclonal antibody has demonstrated safety and efficacy in the salvage treatment of stage IV childhood neuroblastoma, another neuroectodermal tumor. It thus stands to reason that B7-H3 might serve as a therapeutic target in DIPG. B7-H3 immunoreactivity was determined in DIPG and non-diffuse brainstem glioma specimens with immunohistochemistry. In addition, B7-H3 mRNA expression was evaluated with microarrays in another set of specimens. All of the nine (100 %) DIPG specimens were shown to be B7-H3 immunoreactive. In the non-diffuse brainstem glioma group, none of the eight WHO grade I specimens showed B7-H3 immunoreactivity and nine of the 24 WHO grade II specimens (37.5 %) showed B7-H3 immunoreactivity. The association between histological grade and B7-H3 immunoreactivity was statistically highly significant. B7-H3 mRNA expression was also significantly higher in DIPG samples than in normal brain and juvenile pilocytic astrocytoma (WHO grade I) specimens. In summary, B7-H3 is over-expressed in DIPG. Given the need for novel treatment in this disease, antibody-based immunotherapy against B7-H3 in DIPG warrants further investigation.
Insights
Diffuse intrinsic pontine glioma (DIPG), a deadly brain cancer, over-expresses B7-H3. Targeting B7-H3 with immunotherapy shows promise for new DIPG treatments.
Area of Science:
- Neuro-oncology
- Immunology
- Molecular Biology
Background:
- Diffuse intrinsic pontine glioma (DIPG) has a poor prognosis with limited therapeutic options.
- B7-H3 (CD276) is a membrane protein implicated in immune evasion in various cancers.
- B7-H3 is over-expressed in malignant neuroectodermal tumors, including high-grade gliomas.
Purpose of the Study:
- To investigate B7-H3 expression in DIPG specimens.
- To evaluate B7-H3 as a potential therapeutic target for DIPG.
Main Methods:
- Immunohistochemistry was used to assess B7-H3 protein expression in DIPG and non-diffuse brainstem glioma samples.
- Microarray analysis was performed to evaluate B7-H3 mRNA levels in DIPG and control brain tissues.
Main Results:
- 100% of DIPG specimens showed B7-H3 immunoreactivity.
- B7-H3 expression was significantly higher in DIPG compared to non-diffuse brainstem gliomas and normal brain tissue.
- A strong correlation was observed between histological grade and B7-H3 immunoreactivity.
Conclusions:
- B7-H3 is significantly over-expressed in diffuse intrinsic pontine glioma.
- The findings support B7-H3 as a promising therapeutic target for antibody-based immunotherapy in DIPG.
