Abstract
Abstract BACKGROUND H3 K27-altered diffuse midline gliomas (DMG) are highly aggressive malignancies of the central nervous system that affect both pediatric and adult populations. The immune layout and genetic changes within the tumor microenvironment associated with these high-grade malignancies are thought to play an integral role in the phenotypic differences in tumor presentation and clinical course between both populations. Comparative landscapes between pediatric and adult DMGs is not known. METHODS The NanoString GeoMxTM Digital Spatial Profiler platform was used to determine the immune marker and genetic layout in a cohort of both pediatric and adult H3 K27-altered DMG tissue samples. 5 samples from each population were assessed in triplicates for a total of 30 samples. Three fluorescently labeled antibodies targeting immune cells (CD45), epithelial cells (PanCK), tumor cells (H3 K27M) and a nucleic acid stain (SYTO-13) were used to identify and separate out the various components within the tumor tissues from selected regions of interest. The resultant information was then pooled into libraries that were run through the NanoString spatial profiler and Illumina sequencing system to assess proteomics and gene expressions for both cohorts of samples. RESULTS Our data revealed that there were immune and genetic changes that were seen within both populations across multiple regions of interest within the tumor tissues. A number of immune cell types and protein markers exhibited significant difference between the pediatric and adult tissue cohorts. CONCLUSION The proteogenomic spatial analysis of pediatric and adult H3 K27-altered DMG shows different immune and genetic profiles which are proposed to contribute to the clinical differences between both populations. These observed differences may play a role in future treatments for H3 K27-altered DMG and further research is needed to explore this.
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