TMIC-90. Deciphering Microglia-Tumor Development Interactions in Thalamic Pediatric Diffuse Midline Glioma

Abstract Pediatric diffuse midline gliomas (DMGs) are lethal pediatric brain tumors and are the leading cause of brain-tumor related death in children. Pediatric DMGs form in limited brain regions during specific developmental windows, typically in the pons and thalamus during middle childhood. Due to the sensitive location where these tumors are formed, current treatment options are limited with poor prognosis. A primary focus of our research is to understand the developmental cross talk between DMG tumor cells and microglia during tumorigenesis and progression, with the goal of identifying tumor growth drivers and potential therapeutic targets. Toward this goal, we have established a mouse model of thalamic H3K27M-mutant DMG using in utero electroporation (IUE) of the developing thalamus. This strategy allows us to tailor our studies to the time frame when tumors are forming and growing in relation to microglia maturation and activation, which is not yet possible to study in humans. In the current study, we are using this model to identify the molecular mechanisms by which microglia participate in tumor formation and growth in the thalamus. This work can provide valuable insights for future preclinical studies to test efficacy of combinations of clinically relevant treatments for pediatric DMG by targeting specific immune cell types within the tumor microenvironment.