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Modulated Electro-Hyperthermia Facilitates NK-Cell Infiltration and Growth Arrest of Human A2058 Melanoma in a Xenograft Model

Modulated electro-hyperthermia (mEHT), induced by 13.56 MHz radiofrequency, has been demonstrated both in preclinical and clinical studies to efficiently induce tumor damage and complement other treatment modalities. Here, we used a mouse xenograft model of human melanoma (A2058) to test mEHT (~42°C...

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Autores principales: Vancsik, Tamás, Máthé, Domokos, Horváth, Ildikó, Várallyaly, Anett Anna, Benedek, Anett, Bergmann, Ralf, Krenács, Tibor, Benyó, Zoltán, Balogh, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959784/
https://www.ncbi.nlm.nih.gov/pubmed/33732640
http://dx.doi.org/10.3389/fonc.2021.590764
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author Vancsik, Tamás
Máthé, Domokos
Horváth, Ildikó
Várallyaly, Anett Anna
Benedek, Anett
Bergmann, Ralf
Krenács, Tibor
Benyó, Zoltán
Balogh, Andrea
author_facet Vancsik, Tamás
Máthé, Domokos
Horváth, Ildikó
Várallyaly, Anett Anna
Benedek, Anett
Bergmann, Ralf
Krenács, Tibor
Benyó, Zoltán
Balogh, Andrea
author_sort Vancsik, Tamás
collection PubMed
description Modulated electro-hyperthermia (mEHT), induced by 13.56 MHz radiofrequency, has been demonstrated both in preclinical and clinical studies to efficiently induce tumor damage and complement other treatment modalities. Here, we used a mouse xenograft model of human melanoma (A2058) to test mEHT (~42°C) both alone and combined with NK-cell immunotherapy. A single 30 min shot of mEHT resulted in significant tumor damage due to induced stress, marked by high hsp70 expression followed by significant upregulation of cleaved/activated caspase-3 and p53. When mEHT was combined with either primary human NK cells or the IL-2 independent NK-92MI cell line injected subcutaneously, the accumulation of NK cells was observed at the mEHT pretreated melanoma nodules but not at the untreated controls. mEHT induced the upregulation of the chemoattractant CXCL11 and increased the expression of the matrix metalloproteinase MMP2 which could account for the NK-cell attraction into the treated melanoma. In conclusion, mEHT monotherapy of melanoma xenograft tumors induced irreversible heat and cell stress leading to caspase dependent apoptosis to be driven by p53. mEHT could support the intratumoral attraction of distantly injected NK-cells, contributed by CXCL11 and MMP2 upregulation, resulting in an additive tumor destruction and growth inhibition. Therefore, mEHT may offer itself as a good partner for immunotherapy.
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spelling pubmed-79597842021-03-16 Modulated Electro-Hyperthermia Facilitates NK-Cell Infiltration and Growth Arrest of Human A2058 Melanoma in a Xenograft Model Vancsik, Tamás Máthé, Domokos Horváth, Ildikó Várallyaly, Anett Anna Benedek, Anett Bergmann, Ralf Krenács, Tibor Benyó, Zoltán Balogh, Andrea Front Oncol Oncology Modulated electro-hyperthermia (mEHT), induced by 13.56 MHz radiofrequency, has been demonstrated both in preclinical and clinical studies to efficiently induce tumor damage and complement other treatment modalities. Here, we used a mouse xenograft model of human melanoma (A2058) to test mEHT (~42°C) both alone and combined with NK-cell immunotherapy. A single 30 min shot of mEHT resulted in significant tumor damage due to induced stress, marked by high hsp70 expression followed by significant upregulation of cleaved/activated caspase-3 and p53. When mEHT was combined with either primary human NK cells or the IL-2 independent NK-92MI cell line injected subcutaneously, the accumulation of NK cells was observed at the mEHT pretreated melanoma nodules but not at the untreated controls. mEHT induced the upregulation of the chemoattractant CXCL11 and increased the expression of the matrix metalloproteinase MMP2 which could account for the NK-cell attraction into the treated melanoma. In conclusion, mEHT monotherapy of melanoma xenograft tumors induced irreversible heat and cell stress leading to caspase dependent apoptosis to be driven by p53. mEHT could support the intratumoral attraction of distantly injected NK-cells, contributed by CXCL11 and MMP2 upregulation, resulting in an additive tumor destruction and growth inhibition. Therefore, mEHT may offer itself as a good partner for immunotherapy. Frontiers Media S.A. 2021-02-25 /pmc/articles/PMC7959784/ /pubmed/33732640 http://dx.doi.org/10.3389/fonc.2021.590764 Text en Copyright © 2021 Vancsik, Máthé, Horváth, Várallyaly, Benedek, Bergmann, Krenács, Benyó and Balogh http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Vancsik, Tamás
Máthé, Domokos
Horváth, Ildikó
Várallyaly, Anett Anna
Benedek, Anett
Bergmann, Ralf
Krenács, Tibor
Benyó, Zoltán
Balogh, Andrea
Modulated Electro-Hyperthermia Facilitates NK-Cell Infiltration and Growth Arrest of Human A2058 Melanoma in a Xenograft Model
title Modulated Electro-Hyperthermia Facilitates NK-Cell Infiltration and Growth Arrest of Human A2058 Melanoma in a Xenograft Model
title_full Modulated Electro-Hyperthermia Facilitates NK-Cell Infiltration and Growth Arrest of Human A2058 Melanoma in a Xenograft Model
title_fullStr Modulated Electro-Hyperthermia Facilitates NK-Cell Infiltration and Growth Arrest of Human A2058 Melanoma in a Xenograft Model
title_full_unstemmed Modulated Electro-Hyperthermia Facilitates NK-Cell Infiltration and Growth Arrest of Human A2058 Melanoma in a Xenograft Model
title_short Modulated Electro-Hyperthermia Facilitates NK-Cell Infiltration and Growth Arrest of Human A2058 Melanoma in a Xenograft Model
title_sort modulated electro-hyperthermia facilitates nk-cell infiltration and growth arrest of human a2058 melanoma in a xenograft model
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959784/
https://www.ncbi.nlm.nih.gov/pubmed/33732640
http://dx.doi.org/10.3389/fonc.2021.590764
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