Journal Article

B7-H3, a potential therapeutic target, is expressed in diffuse intrinsic pontine glioma

Souweidane, Mark M., Luther, Neal, Hawkins, Cynthia, Handler, Michael H., Zhou, Zhiping, Vibhakar, Rajeev, Ibrahim, George M.

2013

Overview

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.

• Publisher: Springer US,Springer Nature B.V
• Subject: Astrocytoma / B7 Antigens - genetics / B7 Antigens - metabolism / Brain / Brain stem / Brain Stem Neoplasms - metabolism / Brain Stem Neoplasms - pathology / Brain tumors / Child / Child, Preschool / Children / Female / Gene expression / Gene Expression Profiling / Glioma / Glioma - metabolism / Glioma - pathology / Humans / Immunohistochemistry / Immunotherapy / Infant / Laboratory Investigation / Magnetic Resonance Imaging / Male / Medicine / Medicine & Public Health / Membrane proteins / Monoclonal antibodies / Nervous system diseases / Neuroblastoma / Neurology / Oligonucleotide Array Sequence Analysis / Oncology / Retrospective Studies / RNA, Messenger - metabolism / Statistical analysis / Survival / Tomography, X-Ray Computed / Tumors