ArticleThe Journal of clinical investigation2021
Selective glutamine metabolism inhibition in tumor cells improves antitumor T lymphocyte activity in triple-negative breast cancer.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 244 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
244 citing papers in PubMed, 2 syntheses or guidelines pooled it, 337 citations in OpenAlex.
- The role of CD8Frontiers in immunology · 2026Pooled it
- Predicting Immunotherapy Efficacy with Machine Learning in Gastrointestinal Cancers: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2025Pooled it
- Results of the Phase I/II Study and Preliminary B-cell Gene Signature of Combined Inhibition of Glutamine Metabolism and EGFR in Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Mitochondrial mechanisms underlying spatial immune phenotypes in non‑small cell lung cancer: Implications for ICI response and cold‑to‑hot tumor conversion (Review).Oncology reports · 2026Review
- Mitochondrial dynamics: A promising tool for personalized TNBC management.Genes & diseases · 2026Review
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Glutamine Metabolism in Health and Diseases.MedComm · 2026Review
- Beyond conventional therapies: the evolution of targeted agents and immunotherapies in triple-negative breast cancer.Acta pharmacologica Sinica · 2026Review
- The Sleeping Giant: Metabolism and Autophagy in the Generation and Survival of Dormant Polyploid Giant Cancer Cells.MedComm · 2026Review
- Targeting the tumor microenvironment: a new strategy for natural products in breast cancer therapy.Natural products and bioprospecting · 2026Review
- High-Density Type I Collagen Promotes IFN-γAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Short-chain fatty acids act as metabolic and epigenetic regulators in CAR T cell therapy.Molecular therapy. Oncology · 2026Review
- Article
- Illuminating spatial dynamics of glutamine metabolism with a sensitive genetically encoded biosensor.RSC chemical biology · 2026Article
- 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
- Targeting colorectal cancer and T‑cell metabolism for the treatment of colorectal cancer (Review).Oncology reports · 2026Review
- Review
- Decoding T cell exhaustion in the tumour microenvironment.Experimental & molecular medicine · 2026Review
184 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
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Rapidly proliferating tumor and immune cells need metabolic programs that support energy and biomass production. The amino acid glutamine is consumed by effector T cells and glutamine-addicted triple-negative breast cancer (TNBC) cells, suggesting that a metabolic competition for glutamine may exist within the tumor microenvironment, potentially serving as a therapeutic intervention strategy. Here, we report that there is an inverse correlation between glutamine metabolic genes and markers of T cell-mediated cytotoxicity in human basal-like breast cancer (BLBC) patient data sets, with increased glutamine metabolism and decreased T cell cytotoxicity associated with poor survival. We found that tumor cell-specific loss of glutaminase (GLS), a key enzyme for glutamine metabolism, improved antitumor T cell activation in both a spontaneous mouse TNBC model and orthotopic grafts. The glutamine transporter inhibitor V-9302 selectively blocked glutamine uptake by TNBC cells but not CD8+ T cells, driving synthesis of glutathione, a major cellular antioxidant, to improve CD8+ T cell effector function. We propose a "glutamine steal" scenario, in which cancer cells deprive tumor-infiltrating lymphocytes of needed glutamine, thus impairing antitumor immune responses. Therefore, tumor-selective targeting of glutamine metabolism may be a promising therapeutic strategy in TNBC.
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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.