Dissecting Microenvironmental Interactions in Pediatric High-Grade Gliomas that Promote Tumor Growth
Michelle Monje, MD/PhD, Stanford University
The majority of children with high-grade gliomas (HGG) succumb to their disease despite multimodal treatment strategies. To date, most studies on HGGs have focused on whole exome sequencing, DNA methylation, and RNAseq data for disease classification. Far less is known about cell identity changes that contribute to intrinsic and acquired resistance (and treatment failure) and about communication of tumor cells with the microenvironment – both of which are critically important for understanding how tumor cells promote growth and regulate host immunity. Current bulk sequencing approaches have not fully interrogated these critical aspects of the tumor biology and very little has been studied at the level of single-cell analysis. Furthermore, recent publications suggest that single-cell analysis could also be used to study the cell of origin of cancers. If confirmed, these long-missing pieces of information would be critical in opening new therapeutic avenues and designing more clinically-relevant genetically engineered mouse models for pediatric HGGs. Therefore, our overall hypothesis is that a focus on dissecting all cancer cells within a tumor as well as its microenvironment by single-cell RNA sequencing will lead to a better understanding of these diseases and the development of more effective therapeutics to improve outcomes for patients.
Project Update - January 2021: By studying how high-grade glioma cells interact with their environment using a new technology called single-cell RNA-sequencing, we are able to measure what happens in individual cells, as opposed to a cluster of cells. Studying high-grade glioma cells at single-cell resolution may elucidate which mechanisms allow for glioma growth, how the cancer cells remodel their environment to evade the immune system, and consequently may yield new therapeutic approaches.