ArticleThe Journal of clinical investigation2022
Arginine deprivation alters microglial polarity and synergizes with radiation to eradicate non-arginine-auxotrophic glioblastoma tumors.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
53 citing papers in PubMed, 65 citations in OpenAlex.
- A pharmacodynamic study of rapid lactate metabolic modulation by intravenous L-arginine in brain metastases.Frontiers in oncology · 2026Trial
- The Efferocytosis-Driven Macrophage Polarization: A Concerto in the Tumor Immunosuppressive Microenvironment.MedComm · 2026Review
- Sartans and Bisartans: Expanding Therapeutic Horizons Through Broad Receptor Interactions and Repurposing Potential.International journal of molecular sciences · 2026Review
- Glioma microenvironment: Cellular crosstalk, immunosuppression, and novel therapeutic perspectives.Chinese medical journal · 2026Review
- Metabolic Reprogramming in Glioblastoma Stem Cells Promotes Radiation Resistance Through a H3K18la/USP30/MBOAT2 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrative bulk and single-cell analyses implicate ASL in MIF-associated myeloid programs in glioblastoma.Functional & integrative genomics · 2026Article
- Extracellular Vesicles From Glioblastoma Cells Reflect 2D vs. 3D Culture Adaptation and Resistance to Temozolomide.Molecular & cellular proteomics : MCP · 2026Article
- Characterization of blood-brain barrier L-arginine uptake using in situ brain perfusions in a female mouse model.Fluids and barriers of the CNS · 2026Article
- Spatiotemporal dynamics of radioresistance: decoding macrophage-driven radioprotective niches through temporal-spatial reprogramming.Molecular cancer · 2026Review
- MYC-ATF4-ASS1 axis governs intracellular arginine synthesis and dictates the immune microenvironment in melanoma.bioRxiv : the preprint server for biology · 2026Article
- Gut Lachnospiraceae improves white matter injury-related cognitive decline by increasing L-arginine.Cellular & molecular biology letters · 2026Article
- UntargetedTranslational psychiatry · 2026Article
- Arginine Transporters in Human Cancers: Emerging Mechanisms and Clinical Implications.Biomolecules · 2026Review
- Spatiotemporal and metabolic heterogeneity of tumor-associated macrophages in glioblastoma: from single-cell insights to therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Metabolic symbiosis and competition: the dual nature of TAM-tumor cell cross-talk in tumor progression.Frontiers in oncology · 2026Review
- A New Look at the Role of Radiation-Related Epigenetic Mechanisms in Diagnosis and Anticancer Therapies.Cells · 2025Review
- Acute liver failure-induced arginine deficiency impairs blood-brain barrier via inhibiting mTORC1-S6K1/4EBP1 pathway and inducing autophagy.Cell death & disease · 2025Article
- Unlocking Novel Therapeutic Potential of Angiotensin II Receptor Blockers.International journal of molecular sciences · 2025Review
- The therapeutic potential of pegylated arginase I treatment in glioblastoma.Scientific reports · 2025Article
- Arginine Metabolism in Cancer Biology and Immunotherapy.Immune network · 2025Review
Corrections and comments
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Authors and funding
19 authors at 8 institutions in 4 countries.
Funding
Abstract
New approaches for the management of glioblastoma (GBM) are an urgent and unmet clinical need. Here, we illustrate that the efficacy of radiotherapy for GBM is strikingly potentiated by concomitant therapy with the arginine-depleting agent ADI-PEG20 in a non-arginine-auxotrophic cellular background (argininosuccinate synthetase 1 positive). Moreover, this combination led to durable and complete radiological and pathological response, with extended disease-free survival in an orthotopic immune-competent model of GBM, with no significant toxicity. ADI-PEG20 not only enhanced the cellular sensitivity of argininosuccinate synthetase 1-positive GBM to ionizing radiation by elevated production of nitric oxide (˙NO) and hence generation of cytotoxic peroxynitrites, but also promoted glioma-associated macrophage/microglial infiltration into tumors and turned their classical antiinflammatory (protumor) phenotype into a proinflammatory (antitumor) phenotype. Our results provide an effective, well-tolerated, and simple strategy to improve GBM treatment that merits consideration for early evaluation in clinical trials.
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Registered trials
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 OpenQuestion graph.