ArticleNature communications2021
Tumor methionine metabolism drives T-cell exhaustion in hepatocellular carcinoma.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 154 papers.
What it found
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Who cites it
154 citing papers in PubMed, 231 citations in OpenAlex.
- Molecular Mechanisms and Immune Regulation in Prostate Cancer: A Review.International journal of molecular sciences · 2026Review
- Adaptation of Echinococcus Multilocularis to Oxidative Stress Depends on EmPDK-Mediated Metabolic Reprogramming.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- The competition of amino acid among tumors, tumor-associated macrophages and T cells based on metabolic reprogramming.iScience · 2026Review
- Amino Acids as Targets for Immunotherapy against Solid Tumors.Cell biochemistry and biophysics · 2026Review
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- From guardians to traitors: molecular mechanisms of tumor-induced T cell betrayal.Molecular cancer · 2026Review
- Targeting methionine-induced pyroptosis enhances anti-tumor immunity.Science China. Life sciences · 2026Article
- Machine learning integration of multi-omics data develops a sarcomatoid-related renal cell carcinoma score (SARS) for prognosis stratification and guiding therapy.Translational andrology and urology · 2026Article
- Not so cold after all: tumor infiltrating CD8+ T cells in EBV-positive Burkitt lymphoma are quiescent, not exhausted.bioRxiv : the preprint server for biology · 2026Article
- Enteroviral epitope mimicry enables NK cell-mediated targeting of ASPH in hepatocellular carcinoma.bioRxiv : the preprint server for biology · 2026Article
- CD8Cancer cell international · 2026Review
- Multi-omics characterization identifies AHCY as a prognostic biomarker driving immunometabolic reprogramming in bladder cancer.Translational oncology · 2026Article
- Deciphering the MYCN-driven metabolic microenvironment of neuroblastoma.Trends in molecular medicine · 2026Review
- T Cell Exhaustion in Hepatocellular Carcinoma: A Substantial Barrier in Immunotherapy.Journal of cellular and molecular medicine · 2026Review
- Amino Acid Metabolism-Related Gene Kynureninase (KYNU) as a Prognostic Predictor and Regulator of Diffuse Large B-Cell Lymphoma.Biochemical genetics · 2026Article
- Lactate transmission from hypoxic tumor cells promotes macrophage senescence and M2 polarization via the DNMT1-NHE7 axis to accelerate endometrial cancer progression.Cell death & disease · 2026Article
- MAT2A enhances PARN transcription via SRF to accelerate glycolysis and drive malignant progression in osteosarcoma.Communications biology · 2026Article
- Beyond Glucose and Lipids: The Pivotal Role of Amino Acid Reprogramming in Shaping the Tumor Microenvironment and Guiding the Development of Novel Therapeutics.International journal of medical sciences · 2026Review
- Plasma cell-CD8+ T cell co-enrichment distinguishes immunotherapy-responsive hepatocellular carcinoma subtypes.eGastroenterology · 2026Article
94 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
T-cell exhaustion denotes a hypofunctional state of T lymphocytes commonly found in cancer, but how tumor cells drive T-cell exhaustion remains elusive. Here, we find T-cell exhaustion linked to overall survival in 675 hepatocellular carcinoma (HCC) patients with diverse ethnicities and etiologies. Integrative omics analyses uncover oncogenic reprograming of HCC methionine recycling with elevated 5-methylthioadenosine (MTA) and S-adenosylmethionine (SAM) to be tightly linked to T-cell exhaustion. SAM and MTA induce T-cell dysfunction in vitro. Moreover, CRISPR-Cas9-mediated deletion of MAT2A, a key SAM producing enzyme, results in an inhibition of T-cell dysfunction and HCC growth in mice. Thus, reprogramming of tumor methionine metabolism may be a viable therapeutic strategy to improve HCC immunity.
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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.