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Solving the Time- and Frequency-Multiplexed Problem of Constrained Radiofrequency Induced Hyperthermia
Article

Differences of the Immune Phenotype of Breast Cancer Cells after Ex Vivo Hyperthermia by Warm-Water or Microwave Radiation in a Closed-Loop System Alone or in Combination with Radiotherapy

1
Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
2
Chair for Ceramic Materials Engineering, Keylab Glass Technology, University of Bayreuth, 95447 Bayreuth, Germany
3
Biofluid Simulations and Modeling, Fachbereich Physik, University of Bayreuth, 95447 Bayreuth, Germany
4
Dr. Sennewald Medizintechnik GmbH, 81829 Munich, Germany
5
ZIK plasmatis, Leibniz Institute for Plasma Science and Technology, Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany
6
Department of Chemical and Biological Engineering, Institute of Process Machinery and Systems Engineering (iPAT), Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(5), 1082; https://doi.org/10.3390/cancers12051082
Received: 16 March 2020 / Revised: 17 April 2020 / Accepted: 18 April 2020 / Published: 27 April 2020
(This article belongs to the Special Issue Hyperthermia-based Anticancer Treatments)
The treatment of breast cancer by radiotherapy can be complemented by hyperthermia. Little is known about how the immune phenotype of tumor cells is changed thereby, also in terms of a dependence on the heating method. We developed a sterile closed-loop system, using either a warm-water bath or a microwave at 2.45 GHz to examine the impact of ex vivo hyperthermia on cell death, the release of HSP70, and the expression of immune checkpoint molecules (ICMs) on MCF-7 and MDA-MB-231 breast cancer cells by multicolor flow cytometry and ELISA. Heating was performed between 39 and 44 °C. Numerical process simulations identified temperature distributions. Additionally, irradiation with 2 × 5 Gy or 5 × 2 Gy was applied. We observed a release of HSP70 after hyperthermia at all examined temperatures and independently of the heating method, but microwave heating was more effective in cell killing, and microwave heating with and without radiotherapy increased subsequent HSP70 concentrations. Adding hyperthermia to radiotherapy, dynamically or individually, affected the expression of the ICM PD-L1, PD-L2, HVEM, ICOS-L, CD137-L, OX40-L, CD27-L, and EGFR on breast cancer cells. Well-characterized pre-clinical heating systems are mandatory to screen the immune phenotype of tumor cells in clinically relevant settings to define immune matrices for therapy adaption. View Full-Text
Keywords: hyperthermia; microwave-heating; radiotherapy; immunotherapy; breast cancer; immune checkpoint molecules; EGFR; danger signals; immunogenic cancer cell phenotype; multimodal tumor therapies hyperthermia; microwave-heating; radiotherapy; immunotherapy; breast cancer; immune checkpoint molecules; EGFR; danger signals; immunogenic cancer cell phenotype; multimodal tumor therapies
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MDPI and ACS Style

Hader, M.; Savcigil, D.P.; Rosin, A.; Ponfick, P.; Gekle, S.; Wadepohl, M.; Bekeschus, S.; Fietkau, R.; Frey, B.; Schlücker, E.; Gaipl, U.S. Differences of the Immune Phenotype of Breast Cancer Cells after Ex Vivo Hyperthermia by Warm-Water or Microwave Radiation in a Closed-Loop System Alone or in Combination with Radiotherapy. Cancers 2020, 12, 1082. https://doi.org/10.3390/cancers12051082

AMA Style

Hader M, Savcigil DP, Rosin A, Ponfick P, Gekle S, Wadepohl M, Bekeschus S, Fietkau R, Frey B, Schlücker E, Gaipl US. Differences of the Immune Phenotype of Breast Cancer Cells after Ex Vivo Hyperthermia by Warm-Water or Microwave Radiation in a Closed-Loop System Alone or in Combination with Radiotherapy. Cancers. 2020; 12(5):1082. https://doi.org/10.3390/cancers12051082

Chicago/Turabian Style

Hader, Michael, Deniz P. Savcigil, Andreas Rosin, Philipp Ponfick, Stephan Gekle, Martin Wadepohl, Sander Bekeschus, Rainer Fietkau, Benjamin Frey, Eberhard Schlücker, and Udo S. Gaipl. 2020. "Differences of the Immune Phenotype of Breast Cancer Cells after Ex Vivo Hyperthermia by Warm-Water or Microwave Radiation in a Closed-Loop System Alone or in Combination with Radiotherapy" Cancers 12, no. 5: 1082. https://doi.org/10.3390/cancers12051082

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