دورية أكاديمية

Focused Ultrasound Hyperthermia Augments Release of Glioma-derived Extracellular Vesicles with Differential Immunomodulatory Capacity.

التفاصيل البيبلوغرافية
العنوان: Focused Ultrasound Hyperthermia Augments Release of Glioma-derived Extracellular Vesicles with Differential Immunomodulatory Capacity.
المؤلفون: Sheybani ND; Department of Biomedical Engineering; University of Virginia, Charlottesville, VA 22908., Batts AJ; Department of Biomedical Engineering; University of Virginia, Charlottesville, VA 22908., Mathew AS; Department of Biomedical Engineering; University of Virginia, Charlottesville, VA 22908., Thim EA; Department of Biomedical Engineering; University of Virginia, Charlottesville, VA 22908., Price RJ; Department of Biomedical Engineering; University of Virginia, Charlottesville, VA 22908.; Department of Radiology & Medical Imaging, University of Virginia, Charlottesville, VA 22908.
المصدر: Theranostics [Theranostics] 2020 Jun 12; Vol. 10 (16), pp. 7436-7447. Date of Electronic Publication: 2020 Jun 12 (Print Publication: 2020).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Ivyspring International Publisher Country of Publication: Australia NLM ID: 101552395 Publication Model: eCollection Cited Medium: Internet ISSN: 1838-7640 (Electronic) Linking ISSN: 18387640 NLM ISO Abbreviation: Theranostics Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Wyoming, N.S.W. : Ivyspring International Publisher, 2011-
مواضيع طبية MeSH: Extracellular Vesicles/*radiation effects , Glioma/*therapy , High-Intensity Focused Ultrasound Ablation/*methods , Hyperthermia, Induced/*methods, Animals ; Cell Line, Tumor ; Cryoelectron Microscopy ; Dendritic Cells/immunology ; Extracellular Vesicles/immunology ; Extracellular Vesicles/metabolism ; Extracellular Vesicles/ultrastructure ; Glioma/immunology ; Glioma/pathology ; Humans ; Immunity, Innate ; Interleukin-12/immunology ; Interleukin-12/metabolism ; Mice ; Proteomics ; T-Lymphocytes, Helper-Inducer/immunology ; Tumor Escape/radiation effects ; Up-Regulation/radiation effects
مستخلص: Background : Increasing evidence points to the critical role of extracellular vesicles (EVs) as molecular parcels that carry a diverse array of bioactive payloads for coordination of complex intracellular signaling. Focused ultrasound (FUS) hyperthermia is a technique for non-invasive, non-ionizing sublethal heating of cells in a near-instantaneous manner; while it has been shown to improve drug delivery and immunological recognition of tumors, its impact on EVs has not been explored to date. The goal of this study was to determine whether FUS impacts the release, proteomic profile, and immune-activating properties of tumor-derived EVs. Methods: Monolayered murine glioma cells were seeded within acoustically transparent cell culture chambers, and FUS hyperthermia was applied to achieve complete coverage of the chamber. Glioma-derived EVs (GEVs) were isolated for characterization by Nanoparticle Tracking Analysis, cryo-electron microscopy and mass spectrometry. An in vitro experimental setup was designed to further dissect the impact of GEVs on innate inflammation; immortalized murine dendritic cells (DCs) were pulsed with GEVs (either naïve or FUS hyperthermia-exposed) and assayed for production of IL-12p70, an important regulator of DC maturation and T helper cell polarization toward the interferon-γ-producing type 1 phenotype. Results: We confirmed that FUS hyperthermia significantly augments GEV release (by ~46%) as well as shifts the proteomic profile of these GEVs. Such shifts included enrichment of common EV-associated markers, downregulation of markers associated with cancer progression and resistance and modulation of inflammation-associated markers. When DCs were pulsed with GEVs, we noted that naïve GEVs suppressed IL-12p70 production by DCs in a GEV dose-dependent manner. In contrast, GEVs from cells exposed to FUS hyperthermia promoted a significant upregulation in IL-12p70 production by DCs, consistent with a pro-inflammatory stimulus. Conclusion: FUS hyperthermia triggers release of proteomically distinct GEVs that are capable of facilitating an important component of innate immune activation, lending both to a potential mechanism by which FUS interfaces with the tumor-immune landscape and to a role for GEV-associated biomarkers in monitoring response to FUS.
Competing Interests: Competing Interests: The authors have declared that no competing interest exists.
(© The author(s).)
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معلومات مُعتمدة: R01 EB020147 United States EB NIBIB NIH HHS; G20 RR031199 United States RR NCRR NIH HHS; R21 CA226607 United States CA NCI NIH HHS; R01 CA197111 United States CA NCI NIH HHS; F99 CA234954 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Focused ultrasound; cytokine; exosome; extracellular vesicles; glioma
المشرفين على المادة: 187348-17-0 (Interleukin-12)
تواريخ الأحداث: Date Created: 20200710 Date Completed: 20210503 Latest Revision: 20240330
رمز التحديث: 20240330
مُعرف محوري في PubMed: PMC7330848
DOI: 10.7150/thno.46534
PMID: 32642004
قاعدة البيانات: MEDLINE
الوصف
تدمد:1838-7640
DOI:10.7150/thno.46534