Abstract
Medulloblastoma (MB) is the most common malignant brain tumor in children, and has been historically classified based on clinical markers (patient age, presence of metastases at diagnosis, extent of resection) and histopathological characteristics (classic, desmoplastic/nodular, and large cell/anaplastic). However, the recent gene expression profiling of a large number of tumors across multiple studies has provided evidence of four distinct medulloblastoma molecular subgroups (Wnt, Shh, Group 3, and Group 4), associated with remarkably different prognoses. While current therapies for medulloblastoma are often toxic, and not always effective, immunotherapy, designed to target these subgroups, may offer therapeutic improvement. Although monoclonal antibody (mAb) therapy has not yet been shown to be effective for the treatment of brain tumors, recent data indicate that radiation therapy can induce immunogenic modulation characterized by cell-surface phenotypic changes leading to augmented tumour cell/cytotoxic T-cell interaction. We examined the ability of radiation to upregulate mAb therapy targets. Our data showed that low dose radiation significantly increased cell-surface and total protein expression of mAb targets CD137 (a member of the TNF receptor superfamily), FGF, CD20, HER2, Major Histocompatability Complex (MHC) class I and intercellular adhesion molecule-1 (ICAM-I) in 3 out of 3 medulloblastoma cell lines. These findings highlight a mechanism for combining radiation with immunotherapy, to potentially expand the effect of targeted therapy in brain tumor treatment.
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