Childhood Cancer

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Defining the Role of Asthma in the Pathogenesis of Pediatric Brain Tumors

Washington University
Elizabeth Cordell
Grant Type: 
POST Program Grants
Year Awarded: 
Type of Childhood Cancer: 
Brain Tumors
Project Description: 

Mentor: David Gutmann

Gliomas comprise the most common form of brain cancer in both adults and children, where low-grade gliomas (LGGs) are a major etiology for lifelong childhood brain cancer-related morbidity. Currently, the mainstay of glioma treatment involves radiation and/or chemotherapy to target the dividing tumor cells or their deregulated growth control pathways. Unfortunately, these therapies have exhibited inconsistent anti-tumoral effects, especially for childhood LGGs, where they often result in long-term neurocognitive sequelae. Studies from our laboratory and others have revealed that the biology of LGGs are partly dictated by non-neoplastic cells in the tumor microenvironment, including immune system-like cells (microglia, T cells). Using authenticated murine models of LGGs encountered in the Neurofibromatosis type 1 (NF1) pediatric brain tumor predisposition syndrome, we have previously shown that microglia provide essential growth factors necessary for LGG (optic glioma) growth, and that these microglia must be activated by T lymphocytes from the blood. Moreover, provocative evidence from epidemiologic studies has revealed that children with asthma and atopic skin diseases, like eczema, have a two-fold reduced incidence of brain tumors, including children with NF1. Based on these observations, I hypothesize that systemic diseases involving T cells, such as asthma, result in impaired T cell-mediated microglia activation and reduced NF1 optic glioma formation and growth. For this proposal, I have designed experiments to test the hypothesis that asthma impairs T cell activation of microglia important for mouse LGG formation and growth.