The Impact of Metabolic Rewiring in Glioblastoma: The Immune Landscape and Therapeutic Strategies

Glioblastoma (GBM) is an aggressive brain tumor characterized by extensive metabolic reprogramming that drives tumor growth and therapeutic resistance. Key metabolic pathways, including glycolysis, lactate production, and lipid metabolism, are upregulated to sustain tumor survival in the hypoxic and...

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Bibliographic Details
Published in:International journal of molecular sciences Vol. 26; no. 2; p. 669
Main Authors: Vijayanathan, Yuganthini, Ho, Ivy A. W.
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 14.01.2025
MDPI
Subjects:
Adaptation
Adenosine triphosphate
Animals
Brain cancer
Brain Neoplasms - immunology
Brain Neoplasms - metabolism
Brain Neoplasms - pathology
Brain Neoplasms - therapy
Brain tumors
Dehydrogenases
Disease susceptibility
Energy
Enzymes
Epidermal growth factor
Glioblastoma - genetics
Glioblastoma - immunology
Glioblastoma - metabolism
Glioblastoma - pathology
Glioblastoma - therapy
Glioblastoma multiforme
Glioma
Glucose
Glucose metabolism
Glutamine
Health aspects
Humans
Hypoxia
Immunotherapy
Immunotherapy - methods
Kinases
Lipids
Macrophages
Metabolism
Phosphorylation
Physiological aspects
Review
T cells
Tryptophan
Tumor Microenvironment - immunology
glioma
metabolism
GBM
tumor microenvironment
immune infiltration
ISSN:1422-0067, 1661-6596, 1422-0067
Online Access:Get full text
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Summary:Glioblastoma (GBM) is an aggressive brain tumor characterized by extensive metabolic reprogramming that drives tumor growth and therapeutic resistance. Key metabolic pathways, including glycolysis, lactate production, and lipid metabolism, are upregulated to sustain tumor survival in the hypoxic and nutrient-deprived tumor microenvironment (TME), while glutamine and tryptophan metabolism further contribute to the aggressive phenotype of GBM. These metabolic alterations impair immune cell function, leading to exhaustion and stress in CD8+ and CD4+ T cells while favoring immunosuppressive populations such as regulatory T cells (Tregs) and M2-like macrophages. Recent studies emphasize the role of slow-cycling GBM cells (SCCs), lipid-laden macrophages, and tumor-associated astrocytes (TAAs) in reshaping GBM’s metabolic landscape and reinforcing immune evasion. Genetic mutations, including Isocitrate Dehydrogenase (IDH) mutations, Epidermal Growth Factor Receptor (EGFR) amplification, and Phosphotase and Tensin Homolog (PTEN) loss, further drive metabolic reprogramming and offer potential targets for therapy. Understanding the relationship between GBM metabolism and immune suppression is critical for overcoming therapeutic resistance. This review focuses on the role of metabolic rewiring in GBM, its impact on the immune microenvironment, and the potential of combining metabolic targeting with immunotherapy to improve clinical outcomes for GBM patients.
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ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms26020669