ArticleScience translational medicine2025
Tumor extracellular vesicle-derived PD-L1 promotes T cell senescence through lipid metabolism reprogramming.
Article in Science translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Molecular insights into glial neuroimmune cross reactivity with CNS antigens and its role in neuroinflammation.Inflammopharmacology · 2026Pooled it
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- Mechanistic Links Between Natural Bioactive Molecules and Tumor Immune Microenvironment States in PD-1/PD-L1 Resistance.Biomedicines · 2026Review
- Extracellular Vesicles in Cardiovascular Disease: Intercellular Signaling, Liquid Biopsy Biomarkers, and Therapeutic Translation.Circulation research · 2026Review
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- Low-intensity pulsed ultrasound-mediated nose-to-brain co-delivery of β-blockers and aPD-L1 enhances glioblastoma immunotherapy.Nature communications · 2026Article
- Caveolae in cancer: mechanochemical signaling in tumor progression, immunity, and therapy.Cell communication and signaling : CCS · 2026Review
- Eliminating PD-L1 on Dendritic Cell Extracellular Vesicles for Immunotherapy Potentiates Immune-Mediated Tumour Rejection in Mice.Journal of extracellular vesicles · 2026Article
- Potential of RAD51C as a hub gene and therapeutic target in bladder cancer: insights from bioinformatics and experimental analysis.International journal of surgery (London, England) · 2026Article
- Extracellular vesicles in solid tumors: from tumor ecology to engineered therapeutics.Molecular cancer · 2026Review
- Review
- Metabolic Crosstalk Between Host and Tumor as a Circuit of Resilience in Cancer Therapy.Cells · 2026Review
- Lipid metabolism reprogramming shapes the immune landscape in the tumor microenvironment.Cellular & molecular immunology · 2026Review
- METTL16 Promotes Head and Neck Squamous Cell Carcinoma Progression via m6A-Mediated Stabilization of SREBP2 mRNA and Enhanced Cholesterol Biosynthesis.Cancer medicine · 2026Article
- Immune Checkpoint Inhibitors and Immunomodulators for Cancer Immunotherapy: Insights Into Resistance and Therapeutic Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Nanomedicine novel strategies: deciphering the EV-metabolic axis as a natural nanocarrier network in lung cancer progression and cachexia.Journal of nanobiotechnology · 2026Review
- Novel insights into extracellular vesicles: An update on biomolecules, immunomodulation and clinical strategies in skin melanoma.Clinical and translational medicine · 2026Review
- Mitochondria in T‑cell tumor immunity and tumor therapies targeting mitochondria (Review).Oncology reports · 2026Review
- Apoptotic vesicles in cancer: research progress in physiology and therapy.Cell communication and signaling : CCS · 2026Review
- Fatty acid uptake mediated by FABP4 promotes the formation of CD8Oncogenesis · 2026Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
The limited success of cancer immunotherapy has posed challenges in treating patients with cancer. However, promising strides could be made with a deeper understanding of the factors that cause T cell dysfunction within the tumor microenvironment and by developing effective strategies to counteract tumor-induced immune suppression. Here, we report that tumor-derived extracellular vesicles (tEVs) can induce senescence and suppression in T cells. Programmed death ligand 1 (PD-L1), a key component within tEVs, induced DNA damage and hyperactive lipid metabolism in both human and mouse T cells. This caused an elevated expression of lipid metabolic enzymes and an increase in cholesterol and lipid droplet formation, leading to cellular senescence. At a molecular level, PD-L1 derived from tEVs activated the cAMP-response element binding protein (CREB) and signal transducer and activator of transcription (STAT) signaling, which promoted lipid metabolism and facilitated senescence in human and mouse T cells. Inhibiting EV synthesis in tumors or blocking CREB signaling, cholesterol synthesis, and lipid droplet formation in effector T cells averted the tEV-mediated T cell senescence in vitro and in vivo in cell adoptive transfer and melanoma mouse models. The same treatments also bolstered the antitumor efficacy of adoptive transfer T cell therapy and anti-PD-L1 checkpoint immunotherapy in both human and mouse melanoma models. These studies identified mechanistic links between tumor-mediated immune suppression and potential immunotherapy resistance, and they provide new strategies for cancer immunotherapy.
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