High-frequency irreversible electroporation is an effective tumor ablation strategy that induces immunologic cell death and promotes systemic anti-tumor immunity

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dc.contributor.authorRingel-Scaia, Veronica M.en
dc.contributor.authorBeitel-White, Natalieen
dc.contributor.authorLorenzo, Melvin F.en
dc.contributor.authorBrock, Rebecca M.en
dc.contributor.authorHuie, Kathleen E.en
dc.contributor.authorCoutermarsh-Ott, Sherylen
dc.contributor.authorEden, Kristinen
dc.contributor.authorMcDaniel, Dylan K.en
dc.contributor.authorVerbridge, Scott S.en
dc.contributor.authorRossmeisl, John H. Jr.en
dc.contributor.authorOestreich, Kenneth J.en
dc.contributor.authorDavalos, Rafael V.en
dc.contributor.authorAllen, Irving C.en
dc.contributor.departmentElectrical and Computer Engineeringen
dc.contributor.departmentBiomedical Engineering and Mechanicsen
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.contributor.departmentSmall Animal Clinical Sciencesen
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.contributor.departmentInstitute for Critical Technology and Applied Sciencesen
dc.contributor.departmentVirginia Tech Carilion School of Medicineen
dc.date.accessioned2019-10-02T17:27:36Zen
dc.date.available2019-10-02T17:27:36Zen
dc.date.issued2019-06en
dc.description.abstractBackground: Despite promising treatments for breast cancer, mortality rates remain high and treatments for metastatic disease are limited. High-frequency irreversible electroporation (H-FIRE) is a novel tumor ablation technique that utilizes high-frequency bipolar electric pulses to destabilize cancer cell membranes and induce cell death. However, there is currently a paucity of data pertaining to immune system activation following H-FIRE and other electroporation based tumor ablation techniques. Methods: Here, we utilized the mouse 4T1 mammary tumor model to evaluate H-FIRE treatment parameters on cancer progression and immune system activation in vitro and in vivo. Findings: H-FIRE effectively ablates the primary tumor and induces a pro-inflammatory shift in the tumor microenvironment. We further show that local treatment with H-FIRE significantly reduces 4T1 metastases. H-FIRE kills 4T1 cells through non-thermal mechanisms associated with necrosis and pyroptosis resulting in damage associated molecular pattern signaling in vitro and in vivo. Our data indicate that the level of tumor ablation correlates with increased activation of cellular immunity. Likewise, we show that the decrease in metastatic lesions is dependent on the intact immune system and H-FIRE generates 4T1 neoantigens that engage the adaptive immune system to significantly attenuate tumor progression. Interpretation: Cell death and tumor ablation following H-FIRE treatment activates the local innate immune system, which shifts the tumor microenvironment from an anti-inflammatory state to a pro-inflammatory state. The non-thermal damage to the cancer cells and increased innate immune system stimulation improves antigen presentation, resulting in the engagement of the adaptive immune system and improved systemic anti-tumor immunity. (C) 2019 The Authors. Published by Elsevier B.V.en
dc.description.notesThis work was supported by the Virginia-Maryland College of Veterinary Medicine (I.C.A.), the Virginia Tech Institute for Critical Technology and Applied Science Center for Engineered Health (I.C.A.), the Virginia Biosciences Health Research Corporation (VBHRC) Catalyst (R.V.D.), and the National Institutes of Health R01CA213423 (R.V.D. and S.S.V.), P01CA207206 (R.V.D and R.V.D.), R56AI127800 (K.J.O.), and R01AI134972 (K.J.O.). Student work on this publication was supported by the National Institute of Allergy and Infectious Diseases Animal Model Research for Veterinarians (AMRV) training grant (T32-OD010430) (S.C.O. and K.E.) and the American Association of Immunologist Careers in Immunology Fellowship Program (V.M.R.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or any other funding agency.en
dc.description.sponsorshipVirginia-Maryland College of Veterinary Medicine; Virginia Tech Institute for Critical Technology and Applied Science Center for Engineered Health; Virginia Biosciences Health Research Corporation (VBHRC) Catalyst; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01CA213423, P01CA207206, R56AI127800, R01AI134972]; National Institute of Allergy and Infectious Diseases Animal Model Research for Veterinarians (AMRV) training grant [T32-OD010430]; American Association of Immunologist Careers in Immunology Fellowship Programen
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1016/j.ebiom.2019.05.036en
dc.identifier.issn2352-3964en
dc.identifier.pmid31130474en
dc.identifier.urihttp://hdl.handle.net/10919/94322en
dc.identifier.volume44en
dc.language.isoenen
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectIREen
dc.subjectBreast canceren
dc.subjectMetastasisen
dc.subjectTumor microenvironmenten
dc.subjectPyroptosisen
dc.titleHigh-frequency irreversible electroporation is an effective tumor ablation strategy that induces immunologic cell death and promotes systemic anti-tumor immunityen
dc.title.serialEBioMedicineen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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