ArticleCell reports2017
Pharmacologic or Genetic Targeting of Glutamine Synthetase Skews Macrophages toward an M1-like Phenotype and Inhibits Tumor Metastasis.
Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 253 papers.
What it found
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The trial behind it
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Who cites it
253 citing papers in PubMed, 370 citations in OpenAlex.
- Targeting myeloid cell plasticity and metabolic reprogramming to alleviate T cell dysfunction and exhaustion-associated states and enhance immune checkpoint blockade therapy.Biomarker research · 2026Review
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- Reversing Macrophage Immunometabolic Dysfunction in Prolonged Infections Via a Glutaminolysis-Fueled Restoration-Based Hierarchically Selective Therapeutic System.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nanozyme-Mediated Cellular and Microenvironmental Metabolic Reprogramming for Boosting Cancer Immunotherapy.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Unraveling the role of glutamine metabolism in cancer: from cell death mechanisms to tumor microenvironment modulation.Experimental hematology & oncology · 2026Review
- Harnessing macrophage signaling pathways and scalable engineering for next-generation immunotherapies.Signal transduction and targeted therapy · 2026Review
- Gardiquimod Nanoemulsion Targets Cutaneous Leishmaniasis Lesions Reducing Systemic Toxicity and Parasite Burden.Advanced healthcare materials · 2026Article
- Bioengineered systems to exploit tumor microenvironment metabolism.Trends in cancer · 2026Review
- Targeting colorectal cancer and T‑cell metabolism for the treatment of colorectal cancer (Review).Oncology reports · 2026Review
- Emerging roles of ferroptosis in modulating the immune landscape of glial tumours.Nature cell biology · 2026Review
- The competition of amino acid among tumors, tumor-associated macrophages and T cells based on metabolic reprogramming.iScience · 2026Review
- Macrophage Plasticity: Phenotypic and Functional Profiles Across Pathological Microenvironments.International journal of molecular sciences · 2026Review
- Dynamic remodeling of amino acid metabolism in tumor-associated macrophages: Fueling immunosuppression, reshaping tumor niches, and unlocking metabolic checkpoints.Journal of advanced research · 2026Review
- Amino Acids as Targets for Immunotherapy against Solid Tumors.Cell biochemistry and biophysics · 2026Review
- ALDH18A1 regulates glutamine metabolism and tumor microenvironment in the attenuation of clear cell renal cell carcinoma.Cancer cell international · 2026Article
- Review
- Metabolic adaptations of immunosuppressive cells in cancer: mechanisms and therapeutic targets.Experimental & molecular medicine · 2026Review
- Overview of glutamine metabolism in stromal components of the tumor microenvironment and potential anti-tumor therapies.Genes & diseases · 2026Review
- Targeting glutamine metabolism to modulate macrophage functions in the tumor microenvironment.Discover oncology · 2026Review
- Reprogramming of nitrogen metabolism in tumors: mechanisms and therapeutic implications.Amino acids · 2026Review
193 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 4 countries.
Funding
Abstract
Glutamine-synthetase (GS), the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR) activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation. As a result of these metabolic changes and HIF1α accumulation, GS-inhibited macrophages display an increased capacity to induce T cell recruitment, reduced T cell suppressive potential, and an impaired ability to foster endothelial cell branching or cancer cell motility. Genetic deletion of macrophagic GS in tumor-bearing mice promotes tumor vessel pruning, vascular normalization, accumulation of cytotoxic T cells, and metastasis inhibition. These data identify GS activity as mediator of the proangiogenic, immunosuppressive, and pro-metastatic function of M2-like macrophages and highlight the possibility of targeting this enzyme in the treatment of cancer metastasis.
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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.