ArticleCancer immunology research2023
Immunogenetic Metabolomics Reveals Key Enzymes That Modulate CAR T-cell Metabolism and Function.
Article in Cancer immunology research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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
21 citing papers in PubMed.
- Unraveling the immune microenvironment in primary CNS lymphoma.Biomarker research · 2026Review
- Obstacles and improvement strategies for CAR-T cell therapy in solid tumors.Discover oncology · 2026Review
- Translational potential of γδ T cells in hematologic diseases: from immunobiology to therapeutic innovation.Frontiers in immunology · 2026Review
- Review
- Rewiring T Cell Metabolism to Enhance CAR T Cell Function in Solid Tumor Microenvironments.Pharmaceutics · 2025Review
- CAR-T cells in solid tumors: Challenges and breakthroughs.Cell reports. Medicine · 2025Review
- Asparaginase enhances CAR-T cell antitumor immunity by asparagine metabolic reprogramming and central memory induction in ALL.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Current status of chimeric antigen receptor T cell therapy and its exhaustion mechanism.Immunotherapy · 2025Review
- Ginkgolic acid inhibits CD8Journal of pharmaceutical analysis · 2025Article
- Research progress of CD73-adenosine signaling regulating hepatocellular carcinoma through tumor microenvironment.Journal of experimental & clinical cancer research : CR · 2025Review
- New insights on potency assays from recent advances and discoveries in CAR T-cell therapy.Frontiers in immunology · 2025Review
- Research progress on HER2-specific chimeric antigen receptor T cells for immunotherapy of solid tumors.Frontiers in immunology · 2025Review
- Igniting Cold Tumors: Multi-Omics-Driven Strategies to Overcome Immune Evasion and Restore Immune Surveillance.Oncology research · 2025Review
- Metabolic reprogramming of CAR T cells: a new frontier in cancer immunotherapy.Frontiers in immunology · 2025Review
- Comprehensive Analysis of the SUMO-related Signature: Implication for Diagnosis, Prognosis, and Immune Therapeutic Approaches in Cervical Cancer.Biochemical genetics · 2024Article
- Applying metabolic control strategies to engineered T cell cancer therapies.Metabolic engineering · 2024Review
- BCKDK modification enhances the anticancer efficacy of CAR-T cells by reprogramming branched chain amino acid metabolism.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Deciphering the tumor immune microenvironment from a multidimensional omics perspective: insight into next-generation CAR-T cell immunotherapy and beyond.Molecular cancer · 2024Review
- Article
- Selective refueling of CAR T cells using ADA1 and CD26 boosts antitumor immunity.Cell reports. Medicine · 2024Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Immune evasion is a critical step of cancer progression that remains a major obstacle for current T cell-based immunotherapies. Hence, we investigated whether it is possible to genetically reprogram T cells to exploit a common tumor-intrinsic evasion mechanism whereby cancer cells suppress T-cell function by generating a metabolically unfavorable tumor microenvironment (TME). In an in silico screen, we identified ADA and PDK1 as metabolic regulators. We then showed that overexpression (OE) of these genes enhanced the cytolysis of CD19-specific chimeric antigen receptor (CAR) T cells against cognate leukemia cells, and conversely, ADA or PDK1 deficiency dampened this effect. ADA-OE in CAR T cells improved cancer cytolysis under high concentrations of adenosine, the ADA substrate, and an immunosuppressive metabolite in the TME. High-throughput transcriptomics and metabolomics analysis of these CAR T cells revealed alterations of global gene expression and metabolic signatures in both ADA- and PDK1-engineered CAR T cells. Functional and immunologic analyses demonstrated that ADA-OE increased proliferation and decreased exhaustion in CD19-specific and HER2-specific CAR T cells. ADA-OE improved tumor infiltration and clearance by HER2-specific CAR T cells in an in vivo colorectal cancer model. Collectively, these data unveil systematic knowledge of metabolic reprogramming directly in CAR T cells and reveal potential targets for improving CAR T-cell therapy.
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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.