ArticlePloS one2020
Adenosine leakage from perforin-burst extracellular vesicles inhibits perforin secretion by cytotoxic T-lymphocytes.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Metabolic reprogramming and plasticity of cancer stem cells.Frontiers in cell and developmental biology · 2026Review
- Extracellular vesicles as modulators of cancer metabolism and microenvironment.Extracellular vesicles and circulating nucleic acids · 2026Review
- Extracellular Vesicles Derived from Breast Cancer Cells: Emerging Biomarkers of Tumor Progression and Metastasis.Biomolecules · 2025Review
- Effect of Extracellular Vesicles Derived From Tumor Cells on Immune Evasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Metabolic Signaling in the Tumor Microenvironment.Cancers · 2025Review
- Extracellular vesicles may provide an alternative detoxification pathway during skeletal muscle myoblast ageing.Journal of extracellular biology · 2024Article
- Transcriptome analysis of the tardigrade Hypsibius exemplaris exposed to the DNA-damaging agent bleomycin.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2024Article
- Purinergic enzymes on extracellular vesicles: immune modulation on the go.Frontiers in immunology · 2024Review
- Extracellular vesicle-based liquid biopsy biomarkers and their application in precision immuno-oncology.Biomarker research · 2023Review
- NK cells direct the perspective approaches to cancer immunotherapy.Medical oncology (Northwood, London, England) · 2023Review
- Article
- Exploring the Metabolic Differences between Cisplatin- and UV Light-Induced Apoptotic Bodies in HK-2 Cells by an Untargeted Metabolomics Approach.International journal of molecular sciences · 2023Article
- What Inhibits Natural Killers' Performance in Tumour.International journal of molecular sciences · 2022Review
- Comparative Metabolomics of Small Molecules Specifically Expressed in the Dorsal or Ventral Marginal Zones in Vertebrate Gastrula.Metabolites · 2022Article
- The Role of Extracellular Vesicles in Metabolic Reprogramming of the Tumor Microenvironment.Cells · 2022Review
- Metabolomics of small extracellular vesicles derived from isocitrate dehydrogenase 1-mutant HCT116 cells collected by semi-automated size exclusion chromatography.Frontiers in molecular biosciences · 2022Article
- The Role of Exosomes in Cancer Progression.International journal of molecular sciences · 2021Review
- The role of the metabolite cargo of extracellular vesicles in tumor progression.Cancer metastasis reviews · 2021Review
- Current Adenosinergic Therapies: What Do Cancer Cells Stand to Gain and Lose?International journal of molecular sciences · 2021Review
- Metabolomic Analysis of Small Extracellular Vesicles Derived from Pancreatic Cancer Cells Cultured under Normoxia and Hypoxia.Metabolites · 2021Article
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
Extracellular vesicles (EVs) in the tumor microenvironment facilitate intercellular communication. Cancer cell-derived EVs act as an immunosuppressor by transporting cargos and presenting transmembrane proteins. By contrast, CD8+ cytotoxic T-lymphocytes (CTLs) exert anti-cancer cytotoxicity via the pore-forming protein perforin. Here, we hypothesize that although EVs are destroyed by perforin, cancer cell-derived EVs might possess mechanisms that enable them to avoid this destruction. We used a breast cancer cell line, MDA-MB-231-luc-D3H2LN (D3H2LN), to generate EVs. Destruction of the EVs by perforin was demonstrated visually using atomic force microscopy. To investigate immunosuppressive metabolites within cancer cell-derived EVs, we performed metabolomic profiling of EVs from D3H2LN cells cultured for 48 h with or without IFN-γ, which induces metabolic changes in the cells. We found that both types of EV from IFN-γ treated D3H2LN cells and non-treated D3H2LN cells contained adenosine, which has immunosuppressive effects. When we exposed cancer cell-derived EVs to CTLs, perforin secretion by CTLs fell significantly. In addition, the decreases in perforin secretion were ameliorated by treatment with adenosine deaminase, which degrades extracellular adenosine. Taken together, these results suggest that after perforin secreted by CTLs disrupts the membrane of EVs, adenosine released from the EVs acts as an immunosuppressive metabolite by binding to the adenosine receptor on the CTL membrane. This mechanism provides a novel survival strategy using cancer cell-derived EVs.
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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.