ArticleCancer immunology research2024
Metabolic Reprogramming of Tumor-Associated Macrophages Using Glutamine Antagonist JHU083 Drives Tumor Immunity in Myeloid-Rich Prostate and Bladder Cancers.
Article in Cancer immunology research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed.
- Tumor‑immune spatiotemporal co‑evolution: A new paradigm for understanding and overcoming therapy resistance in metastatic castration‑resistant prostate cancer (Review).International journal of molecular medicine · 2026Review
- Decoding the metabolic‑immune crosstalk: The role of glutamine and ammonium reprogramming in prostate cancer immune evasion (Review).Oncology reports · 2026Review
- The Cancer Cell Metabolic Reprogramming Remodels the Tumor Microenvironment: Molecular Mechanisms and Therapeutic Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Unraveling the role of glutamine metabolism in cancer: from cell death mechanisms to tumor microenvironment modulation.Experimental hematology & oncology · 2026Review
- Review
- A machine learning-guided epithelial plasticity score refines prognostication and immune-context stratification in muscle-invasive bladder cancer.Discover oncology · 2026Article
- 70 Years of DON and Beyond: Glutaminase Inhibition as a Synergistic Strategy in Cancer Combination Therapy.Pharmaceutics · 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
- Leveraging Macrophage Metabolic Reprogramming for Enhanced Anti-Tumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Acetylated mitochondrial MDH2 regulates CTR2 transcription to induce cuproptosis during Escherichia coli infection.Nature communications · 2026Article
- Metabolic pattern changes of macrophages during cancer development and progression.Journal of translational medicine · 2026Review
- Targeting glutamine metabolism to modulate macrophage functions in the tumor microenvironment.Discover oncology · 2026Review
- Metabolic regulation of tumor-associated macrophage function and immunotherapy in cancer.Cancer biology & medicine · 2026Review
- Cigarette Smoking-RegulatedEnvironment & health (Washington, D.C.) · 2026Article
- ACSL5 Regulates Glucose Metabolism and Chemotherapy Sensitivity in Colorectal Cancer Cells under Glutamine Deficiency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Glutamine synthetase deficiency enhances CD8 T cell survival and stress resilience in the tumor microenvironment.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Pan-cancer bone metastasis atlas at single-cell resolution identifies a distinct tumor-associated macrophage subset for mediating Denosumab-induced immunosensitization in lung cancer bone metastasis.International journal of biological sciences · 2026Article
- Metabolic symbiosis and competition: the dual nature of TAM-tumor cell cross-talk in tumor progression.Frontiers in oncology · 2026Review
- The Quartet of Core Oncogenic Drivers in Neuroendocrine Prostate Cancer: Multi-Omics Dataset Integration to Forge a Translational Link Between Biology and Precision Therapy.International journal of biological sciences · 2026Review
- Immunometabolic programming of macrophages and tumor-associated macrophages: metabolic pathways shaping polarization, immune regulation, and disease outcomes.Frontiers in immunology · 2026Review
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Authors and funding
23 authors.
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Abstract
Glutamine metabolism in tumor microenvironments critically regulates antitumor immunity. Using the glutamine-antagonist prodrug JHU083, we report potent tumor growth inhibition in urologic tumors by JHU083-reprogrammed tumor-associated macrophages (TAMs) and tumor-infiltrating monocytes. We show JHU083-mediated glutamine antagonism in tumor microenvironments induced by TNF, proinflammatory, and mTORC1 signaling in intratumoral TAM clusters. JHU083-reprogrammed TAMs also exhibited increased tumor cell phagocytosis and diminished proangiogenic capacities. In vivo inhibition of TAM glutamine consumption resulted in increased glycolysis, a broken tricarboxylic acid (TCA) cycle, and purine metabolism disruption. Although the antitumor effect of glutamine antagonism on tumor-infiltrating T cells was moderate, JHU083 promoted a stem cell-like phenotype in CD8+ T cells and decreased the abundance of regulatory T cells. Finally, JHU083 caused a global shutdown in glutamine-utilizing metabolic pathways in tumor cells, leading to reduced HIF-1α, c-MYC phosphorylation, and induction of tumor cell apoptosis, all key antitumor features. Altogether, our findings demonstrate that targeting glutamine with JHU083 led to suppressed tumor growth as well as reprogramming of immunosuppressive TAMs within prostate and bladder tumors that promoted antitumor immune responses. JHU083 can offer an effective therapeutic benefit for tumor types that are enriched in immunosuppressive TAMs.
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