Authors:

Miruna Anica

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About Paper:

Glioblastoma (GBM) is the most aggressive form of brain cancer, with only 6% of patients surviving for 5 years or longer post-diagnosis. There is a dire need to better understand tumor heterogeneity and the tumor microenvironment (TME) to develop therapies that effectively target the interaction between tumor and immune cells. Our group has characterized two cell populations, fast-cycling cells (FCCs) harnessing aerobic glycolysis, and treatment-resistant slow-cycling cancer stem cells (SCCs) engaging in lipid metabolism. Murine and human glioma tissues were analyzed using geospatial profiling techniques, where it was found that SCCs induce an immunosuppressive microenvironment by recruiting macrophages and MDSCs, where the FCC microenvironment is upregulated with cytotoxic T cells. Microscopy and flow cytometry were utilized to better understand the mechanisms by which SCCs reshape their milieu by recruiting tumorigenic immune cells. SCCs have been observed to induce lipid transfer from macrophages, thereby increasing fatty-acid uptake to provide a survival advantage in the nutrient-deplete environment characteristic of GBM. These mechanisms play a critical role in the progression of GBM and treatment- resistant tumors. 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. These insights delineate potential therapeutic effects of disrupting SCC-induced metabolic pathways to shape a TME that is more responsive to treatment. Our future work will focus on further elucidating the communicative pathways between SCCs and macrophages.

Source:

University of Florida / Miruna Anica, Diana Feier, Aryeh Silver, Avirup / 2023

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Co-authors:

Miruna Anica