ArticleJournal of extracellular vesicles2022
Impact on NK cell functions of acute versus chronic exposure to extracellular vesicle-associated MICA: Dual role in cancer immunosurveillance.
Article in Journal of extracellular vesicles, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 62 citations in OpenAlex.
- Extracellular Vesicles as Master Regulators of Immune Modulation in Multiple Myeloma.International journal of molecular sciences · 2026Review
- Engineered extracellular vesicles for combinatorial cancer therapy and imaging.Acta pharmaceutica Sinica. B · 2026Review
- Targeting the MICA/B-NKG2D axis in cancer: from molecular structure to immunotherapeutic strategies-a narrative review.Translational cancer research · 2026Review
- Multiphysics-Driven Assembly of Biomimetic Vesicles.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- The avatar principle: exosomal dynamics guiding tumor adaptation and next-generation therapeutic strategies.Journal of nanobiotechnology · 2026Review
- Novel perspectives on extracellular vesicles in autoimmune diseases: immunogenicity, inflammation, and immune surveillance.The Journal of clinical investigation · 2026Review
- Insights into ectodomain shedding as a novel target in natural killer cell-based immunotherapy for cancer.Frontiers in immunology · 2026Review
- Extracellular vesicles in multiple myeloma-bone marrow niche crosstalk: from cellular dialogue to clinical perspectives.Journal of translational medicine · 2025Review
- From Combination Early Detection to Multicancer Testing: Shifting Cancer Care toward Proactive Prevention and Interception.Cancer prevention research (Philadelphia, Pa.) · 2025Review
- Extracellular vesicles in cancer immunotherapy: Therapeutic, challenges and clinical progress.Asian journal of pharmaceutical sciences · 2025Review
- Extracellular vesicles: biogenesis mechanism and impacts on tumor immune microenvironment.Journal of biomedical science · 2025Review
- Association ofZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- Effect of Extracellular Vesicles Derived From Tumor Cells on Immune Evasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Exosome-mediated Crosstalk in the Tumor Immune Microenvironment: Critical Drivers of Hepatocellular Carcinoma Progression.Journal of clinical and translational hepatology · 2025Review
- Tumor-derived extracellular vesicles mediate cell-specific uptake and facilitate enhanced doxorubicin delivery in breast cancer.Frontiers in pharmacology · 2025Article
- NKG2D triggering hampers DNAM-1-mediated signaling in human NK cells.Frontiers in immunology · 2025Article
- Tumor-derived exosomes as promising tools for cancer diagnosis and therapy.Frontiers in pharmacology · 2025Review
- Two major human phenotypes of MICA molecules and their differential activation to NK cells via NKG2D receptor.Frontiers in immunology · 2025Article
- Deciphering the bone marrow microenvironment's role in multiple myeloma immunotherapy resistance.Frontiers in immunology · 2025Review
- Extracellular Vesicles from Mesenchymal Stem Cells: Potential as Therapeutics in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).Biomedicines · 2024Review
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural killer (NK) cells are innate cytotoxic lymphocytes that play a key role in cancer immunosurveillance thanks to their ability to recognize and kill cancer cells. NKG2D is an activating receptor that binds to MIC and ULBP molecules typically induced on damaged, transformed or infected cells. The release of NKG2D ligands (NKG2DLs) in the extracellular milieu through protease-mediated cleavage or by extracellular vesicle (EV) secretion allows cancer cells to evade NKG2D-mediated immunosurveillance. In this work, we investigated the immunomodulatory properties of the NKG2D ligand MICA*008 associated to distinct populations of EVs (i.e., small extracellular vesicles [sEVs] and medium size extracellular vesicles [mEVs]). By using as model a human MICA*008-transfected multiple myeloma (MM) cell line, we found that this ligand is present on both vesicle populations. Interestingly, our findings reveal that NKG2D is specifically involved in the uptake of vesicles expressing its cognate ligand. We provide evidence that MICA*008-expressing sEVs and mEVs are able on one hand to activate NK cells but, following prolonged stimulation induce a sustained NKG2D downmodulation leading to impaired NKG2D-mediated functions. Moreover, our findings show that MICA*008 can be transferred by vesicles to NK cells causing fratricide. Focusing on MM as a clinically and biologically relevant model of tumour-NK cell interactions, we found enrichment of EVs expressing MICA in the bone marrow of a cohort of patients. All together our results suggest that the accumulation of NKG2D ligands associated to vesicles in the tumour microenvironment could favour the suppression of NK cell activity either by NKG2D down-modulation or by fratricide of NK cell dressed with EV-derived NKG2D ligands.
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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.