ArticleJCI insight2023
Modulating the polyamine/hypusine axis controls generation of CD8+ tissue-resident memory T cells.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- A systematic transcriptomic atlas and predictive framework for metabolite-driven T cell state transitions.iScience · 2026Article
- Epigenetic reprogramming of T cell metabolism restores function and enhances anti-tumor immunity in lung cancer.Nature immunology · 2026Article
- HDAC7 controls anti-viral and anti-tumor immunity by CD8Frontiers in immunology · 2026Article
- Dysbiosis modulates CD8iScience · 2025Article
- Oncobiomics: Leveraging Microbiome Translational Research in Immuno-Oncology for Clinical-Practice Changes.Biomolecules · 2025Review
- Immunogenic shift of arginine metabolism triggers systemic metabolic and immunological reprogramming to suppress HER2 + breast cancer.Cancer & metabolism · 2025Article
- Assessing the Role of Polyamine Metabolites in Blood and the DNA Methylation ofInternational journal of medical sciences · 2025Article
- Challenges in the preclinical design and assessment of CAR-T cells.Frontiers in immunology · 2025Review
- Optimizing CAR-T cell therapy for solid tumors: current challenges and potential strategies.Journal of hematology & oncology · 2024Review
- Optimizing CD8Experimental hematology & oncology · 2024Review
- Impact the impact of gut microbiota on gastric cancer via immune cells: a comprehensive Mendelian randomization study and mediation analysis.Discover oncology · 2024Article
- Polyamines: the pivotal amines in influencing the tumor microenvironment.Discover oncology · 2024Review
- Mucosal microbiota characterization in gastric cancer identifies immune-activated-related transcripts relevant gastric microbiome signatures.Frontiers in immunology · 2024Article
- T cell metabolism in kidney immune homeostasis.Frontiers in immunology · 2024Review
- Crosstalk between efferocytic myeloid cells and T-cells and its relevance to atherosclerosis.Frontiers in immunology · 2024Review
- Polyamines: Key Players in Immunometabolism and Immune Regulation.Journal of cellular immunology · 2024Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Glutaminolysis is a hallmark of the activation and metabolic reprogramming of T cells. Isotopic tracer analyses of antigen-activated effector CD8+ T cells revealed that glutamine is the principal carbon source for the biosynthesis of polyamines putrescine, spermidine, and spermine. These metabolites play critical roles in activation-induced T cell proliferation, as well as for the production of hypusine, which is derived from spermidine and is covalently linked to the translation elongation factor eukaryotic translation initiation factor 5A (eIF5A). Here, we demonstrated that the glutamine/polyamine/hypusine axis controlled the expression of CD69, an important regulator of tissue-resident memory T cells (Trm). Inhibition of this circuit augmented the development of Trm cells ex vivo and in vivo in the BM, a well-established niche for Trm cells. Furthermore, blocking the polyamine/hypusine axis augmented CD69 expression as well as IFN-γ and TNF-α production in (a) human CD8+ T cells from peripheral blood and sarcoma tumor infiltrating lymphocytes and (b) human CD8+ CAR-T cells. Collectively, these findings support the notion that the polyamine-hypusine circuit can be exploited to modulate Trm cells for therapeutic benefit.
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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.