Abstract
Abstract Glioblastoma (GBM) contains cell populations with distinct metabolic requirements, with fast-cycling cells (FCCs) harnessing aerobic glycolysis, and treatment-resistant slow-cycling cancer stem cells (SCCs) preferentially engaging in lipid metabolism. The interaction between immune and tumor cells, and how tumor metabolic heterogeneity shapes the immune landscape in GBM has yet to be understood. Our study allows for the molecular and spatial decoding of the heterogeneity within the GBM microenvironment, with a specific focus on unraveling the metabolic links that underlie the interplay between SCCs and the immune compartment. Our work indicates a new paradigm of communication in the TME of GBM, where SCCs play a pivotal role in shifting the tumor milieu toward an immunosuppressive phenotype, in part by recruiting specific tumor-promoting immune cells that stimulate SCC-driven tumor progression and provide metabolic support to these treatment-resistant cells. Our study delineates these metabolic communications and assesses the potential therapeutic effect of disrupting these interactions to treat GBM. The insights generated from this project uncover fundamental principles of the emerging connections between the tumor microenvironment, cell metabolism, anti-tumor immunity, and associated therapeutic vulnerabilities. In conclusion, our study provides a novel understanding of the role of metabolic interactions in the development of drug and immune resistant GBM. These findings suggest that targeting metabolic interactions, specifically between SCCs and tumor-associated immune suppressive cells, may be a promising therapeutic strategy for GBM.
Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
