ArticleProceedings of the National Academy of Sciences of the United States of America2023
Tumor cell-derived spermidine is an oncometabolite that suppresses TCR clustering for intratumoral CD8
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 51 citations in OpenAlex.
- Arginine metabolism, polyamine homeostasis and ferroptosis in cancer: Molecular links and therapeutic opportunities (Review).Molecular medicine reports · 2026Review
- Article
- Polyamines in CNS malignancies: positively charged culprits in the hijacking of neural and immune signaling pathways.Amino acids · 2026Review
- LC-QQQ serum metabolomics reveals disease-specific metabolic signatures and diagnostic metabolite panels distinguishing polycythaemia vera from secondary polycythaemia.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- The competition of amino acid among tumors, tumor-associated macrophages and T cells based on metabolic reprogramming.iScience · 2026Review
- Loss of Arginase 2 Promotes Lung Metastasis in immune-competent hosts via Nitric Oxide Synthase 2-Dependent Th17 Response.bioRxiv : the preprint server for biology · 2026Article
- Metabolites as signalling molecules in the tumour immune microenvironment.Nature reviews. Immunology · 2026Review
- Deciphering the MYCN-driven metabolic microenvironment of neuroblastoma.Trends in molecular medicine · 2026Review
- Article
- Redox-metabolic circuits as a central regulator of T cell-based immunotherapy.Frontiers in immunology · 2026Review
- Metabolic syndrome promotes endometrial cancer by Oleic acid-mediated polyamine accumulation.Nature communications · 2025Article
- Evodiamine Inhibits Colorectal Cancer by Downregulating ASS1 via Wnt/β-Catenin/c-MYC Pathway to Block Arginine Synthesis.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Engineered spermidine-secreting Saccharomyces boulardii ameliorates colitis and colon cancer in mice.Scientific reports · 2025Article
- Lipid Metabolism Reprogramming in Cancer: Insights into Tumor Cells and Immune Cells Within the Tumor Microenvironment.Biomedicines · 2025Review
- Prognostic poteintial of polyamine metabolism-related genes in hepatocellular carcinoma.Scientific reports · 2025Article
- Metabolomic reprogramming of the tumor microenvironment by dual arginase inhibitor OATD-02 boosts anticancer immunity.Scientific reports · 2025Article
- The biological activity and potential of probiotics-derived extracellular vesicles as postbiotics in modulating microbiota-host communication.Journal of nanobiotechnology · 2025Review
- Methionine Metabolism Dictates PCSK9 Expression and Antitumor Potency of PD-1 Blockade in MSS Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Plasma protein levels and hepatocellular carcinoma: a Mendelian randomization study with drug screening implications.Discover oncology · 2025Article
- Antitumor potential of polyamines in cancer.Acta biochimica et biophysica Sinica · 2025Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The activation and expansion of T cells that recognize cancer cells is an essential aspect to antitumor immunity. Tumors may escape destruction by the immune system through ectopic expression of inhibitory immune ligands typically exemplified by the PD-L1/PD-1 pathway. Here, we reveal another facet of tumor evasion from T cell surveillance. By secretome profiling of necrotic tumor cells, we identified an oncometabolite spermidine as a unique inhibitor of T cell receptor (TCR) signaling. Mechanistically, spermidine causes the downregulation of the plasma membrane cholesterol levels, resulting in the suppression of TCR clustering. Using syngeneic mouse models, we show that spermidine is abundantly detected in the tumor immune microenvironment (TIME) and that administration of the polyamine synthesis inhibitor effectively enhanced CD8
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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.