TMET-10. INVESTIGATING HOW GLIOBLASTOMA TUMOUR CELLS EXPLOIT THEIR METABOLIC MICROENVIRONMENT

Abstract

Abstract A significant challenge in neuro-oncology is identifying the metabolic fuel sources that underpin glioblastoma malignancy. Metabolic reprogramming is a hallmark of tumorigenesis, providing malignant cells with an adaptation advantage to survive and grow under environmental stresses, including anti-cancer therapies. Incorporating single-cell RNA sequencing data from 56 glioblastoma patient biopsies, we have identified distinct subpopulations of malignant cells which diverge in their metabolic activities. These metabolic subpopulations are conserved across patient datasets but vary in abundance from patient to patient, contributing to glioblastoma heterogeneity. We are also employing spatial transcriptomics to build a map of the metabolic tumour landscape. This analysis showed that these malignant sub-populations occupy distinct spatial regions in the tumour landscape. Environmental influences like distance to blood vessels, which impact oxygen and nutrient supply, can vary significantly between regions. This suggests that as malignant cells colonise different regions of the tumour, they modify their metabolism as an adaption response. Importantly these niches vary in their compositions of native brain and immune cells, contributing to the diverse ecosystems inhabited by these malignant subpopulations. The next steps are to explore the specific metabolite dependencies of these tumour cells by mass spectrometry imaging and identify metabolite fluxes within the microenvironment that we can target therapeutically.