ArticleJournal of immunology (Baltimore, Md. : 1950)2023
Differential Effects of Glutamine Inhibition Strategies on Antitumor CD8 T Cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 24 citations in OpenAlex.
- Glutamine antagonist DON attenuates chikungunya virus-induced myositis by suppressing inflammatory activation in a murine model.Emerging microbes & infections · 2026Article
- Multiomic analysis identifies glutaminolysis-dependent metabolic enhancement of immune memory utilised for vaccine development.Nature communications · 2026Article
- T cell fate regulation in EBV‑associated nasopharyngeal carcinoma (Review).Oncology reports · 2026Review
- The role of tumor metabolic reprogramming in acquired anti-PD-1/PD-L1 resistance.Translational lung cancer research · 2026Review
- Reprogramming of nitrogen metabolism in tumors: mechanisms and therapeutic implications.Amino acids · 2026Review
- Tissue and CD4 T cell subset dependence on the amino acid transporter SLC38A1.Cell metabolism · 2026Article
- Glutamine synthetase deficiency enhances CD8 T cell survival and stress resilience in the tumor microenvironment.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Integrating T cell signaling and metabolism to enhance T cell engager responses in solid tumors.Frontiers in immunology · 2026Review
- The cellular senescence-metabolism axis: emerging insights into T cell dynamics in the context of biological aging.Cell communication and signaling : CCS · 2025Review
- Targeted Metabolomic Methods forJournal of proteome research · 2025Article
- Integrated bioinformatics analysis identifies cuproptosis and ferroptosis gene signatures via subgroup clustering: Prognostic and therapeutic implications in breast cancer.Biochemistry and biophysics reports · 2025Article
- Metabolic checkpoints in immune cell reprogramming: rewiring immunometabolism for cancer therapy.Molecular cancer · 2025Review
- Mitochondrial fatty acid synthesis and MECR regulate CD4+ T cell function and oxidative metabolism.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Metabolism of Tryptophan, Glutamine, and Asparagine in Cancer Immunotherapy-Synergism or Mechanism of Resistance?Metabolites · 2025Review
- Review
- Glutamine metabolism and ammonia death: targeted modulation for enhanced cancer immunotherapy.Frontiers in immunology · 2025Review
- Metabolism of tumor infiltrating T cells.Frontiers in immunology · 2025Review
- Immunometabolic Maladaptations to the Tumor Microenvironment.Cold Spring Harbor perspectives in medicine · 2024Review
- Current Landscape of Cancer Immunotherapy: Harnessing the Immune Arsenal to Overcome Immune Evasion.Biology · 2024Review
- A glutamine tug-of-war between cancer and immune cells: recent advances in unraveling the ongoing battle.Journal of experimental & clinical cancer research : CR · 2024Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
Activated T cells undergo metabolic reprogramming to meet anabolic, differentiation, and functional demands. Glutamine supports many processes in activated T cells, and inhibition of glutamine metabolism alters T cell function in autoimmune disease and cancer. Multiple glutamine-targeting molecules are under investigation, yet the precise mechanisms of glutamine-dependent CD8 T cell differentiation remain unclear. We show that distinct strategies of glutamine inhibition by glutaminase-specific inhibition with small molecule CB-839, pan-glutamine inhibition with 6-diazo-5-oxo-l-norleucine (DON), or by glutamine-depleted conditions (No Q) produce distinct metabolic differentiation trajectories in murine CD8 T cells. T cell activation with CB-839 treatment had a milder effect than did DON or No Q treatment. A key difference was that CB-839-treated cells compensated with increased glycolytic metabolism, whereas DON and No Q-treated cells increased oxidative metabolism. However, all glutamine treatment strategies elevated CD8 T cell dependence on glucose metabolism, and No Q treatment caused adaptation toward reduced glutamine dependence. DON treatment reduced histone modifications and numbers of persisting cells in adoptive transfer studies, but those T cells that remained could expand normally upon secondary Ag encounter. In contrast, No Q-treated cells persisted well yet demonstrated decreased secondary expansion. Consistent with reduced persistence, CD8 T cells activated in the presence of DON had reduced ability to control tumor growth and reduced tumor infiltration in adoptive cell therapy. Overall, each approach to inhibit glutamine metabolism confers distinct effects on CD8 T cells and highlights that targeting the same pathway in different ways can elicit opposing metabolic and functional outcomes.
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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.