ArticleThe Journal of clinical investigation2024
Tumor cell-derived spermidine promotes a protumorigenic immune microenvironment in glioblastoma via CD8+ T cell inhibition.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- The Microbiome in Glioblastoma: Mechanisms, Tumor-Immune Interactions, and Translational Perspectives.MicrobiologyOpen · 2026Review
- TRPV4 is Associated with a Marfan Syndrome-Related Mechanosensitive Gene Program in Aortic Smooth Muscle Cells.Biochemical genetics · 2026Article
- DHCR24 regulates endothelial senescence through the SPHK2/SPNS2-S1P axis.Biogerontology · 2026Article
- The Cancer Cell Metabolic Reprogramming Remodels the Tumor Microenvironment: Molecular Mechanisms and Therapeutic Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- SpaMTP: integrative statistical analysis and visualization of spatial metabolomics and transcriptomics data.Nature methods · 2026Article
- Polyamines in CNS malignancies: positively charged culprits in the hijacking of neural and immune signaling pathways.Amino acids · 2026Review
- Development and characterization of triazole-based WDR5 inhibitors for the treatment of glioblastoma.JCI insight · 2026Article
- PRMT3-Mediated Arginine Methylation Stabilizes PCSK9 to Promote Aortic Valve Calcification.Circulation · 2026Article
- Blood-Brain Barrier (BBB)-Penetrable Androgen Receptor (AR) Degrader as a Potential Therapeutic Agent for Glioblastoma.ACS pharmacology & translational science · 2026Article
- Spermidine and Eugenol Modulate Tight Junction and Stemness Markers in Colorectal Cancer Spheroids.International journal of molecular sciences · 2026Article
- cRGD-Functionalized macrophage extracellular vesicles loaded with GSK2033 enhance T cell antitumor immunity in GBM by disrupting the LXR/ABCA1-Mediated Myelin lipid transfer axis.Journal of nanobiotechnology · 2026Article
- Polyamine Metabolism in Brain Health and Disease.Neuropharmacology and therapy · 2026Article
- Defining treatment-resistant brain cancer: Genetic screening to identify oncogene-driven immunomodulation and therapy resistance.Cancer gene therapy · 2026Review
- Mitochondrial transfer: a new perspective on tumor-microenvironment crosstalk driving metastasis.Frontiers in immunology · 2026Review
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
- Gut microbial metabolites in cancer immunomodulation.Molecular cancer · 2025Review
- Polyamine metabolism in cancer: drivers of immune evasion, ferroptosis and therapy resistance.Expert reviews in molecular medicine · 2025Review
- Receptor-Mediated Internalization of L-Asparaginase into Tumor Cells Is Suppressed by Polyamines.International journal of molecular sciences · 2025Article
- Microbial metabolite-driven immune reprogramming in tumor immunotherapy: mechanisms and therapeutic perspectives.Frontiers in immunology · 2025Review
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Authors and funding
26 authors.
Funding
Abstract
The glioblastoma (GBM) microenvironment is enriched in immunosuppressive factors that potently interfere with the function of cytotoxic T lymphocytes. Cancer cells can directly affect the immune system, but the mechanisms driving these interactions are not completely clear. Here, we demonstrate that the polyamine metabolite spermidine (SPD) was elevated in the GBM tumor microenvironment. Exogenous administration of SPD drove tumor aggressiveness in an immune-dependent manner in preclinical mouse models via reduction of CD8+ T cell frequency and reduced cytotoxic function. Knockdown of ornithine decarboxylase, the rate-limiting enzyme in SPD synthesis, did not affect cancer cell growth in vitro but did result in extended survival. Furthermore, patients with GBM with a more favorable outcome had a significant reduction in SPD compared with patients with a poor prognosis. Our results demonstrate that SPD functions as a cancer cell-derived metabolite that drives tumor progression by reducing CD8+ T cell numbers and function.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.