High-frequency irreversible electroporation is an effective tumor ablation strategy that induces immunologic cell death and promotes systemic anti-tumor immunity. Ringel-Scaia, V. M., Beitel-White, N., Lorenzo, M. F., Brock, R. M., Huie, K. E., Coutermarsh-Ott, S., Eden, K., McDaniel, D. K., Verbridge, S. S., Rossmeisl, J. H., Oestreich, K. J., Davalos, R. V., & Allen, I. C. EBioMedicine, 44:112-125, 2019. 2352-3964 Ringel-Scaia, Veronica M Beitel-White, Natalie Lorenzo, Melvin F Brock, Rebecca M Huie, Kathleen E Coutermarsh-Ott, Sheryl Eden, Kristin McDaniel, Dylan K Verbridge, Scott S Rossmeisl, John H Jr Oestreich, Kenneth J Davalos, Rafael V Allen, Irving C R01 AI134972/AI/NIAID NIH HHS/United States R56 AI127800/AI/NIAID NIH HHS/United States Journal Article Netherlands 2019/05/28 EBioMedicine. 2019 Jun;44:112-125. doi: 10.1016/j.ebiom.2019.05.036. Epub 2019 May 23.doi abstract bibtex BACKGROUND: 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.
@article{RN148,
author = {Ringel-Scaia, V. M. and Beitel-White, N. and Lorenzo, M. F. and Brock, R. M. and Huie, K. E. and Coutermarsh-Ott, S. and Eden, K. and McDaniel, D. K. and Verbridge, S. S. and Rossmeisl, J. H., Jr. and Oestreich, K. J. and Davalos, R. V. and Allen, I. C.},
title = {High-frequency irreversible electroporation is an effective tumor ablation strategy that induces immunologic cell death and promotes systemic anti-tumor immunity},
journal = {EBioMedicine},
volume = {44},
pages = {112-125},
note = {2352-3964
Ringel-Scaia, Veronica M
Beitel-White, Natalie
Lorenzo, Melvin F
Brock, Rebecca M
Huie, Kathleen E
Coutermarsh-Ott, Sheryl
Eden, Kristin
McDaniel, Dylan K
Verbridge, Scott S
Rossmeisl, John H Jr
Oestreich, Kenneth J
Davalos, Rafael V
Allen, Irving C
R01 AI134972/AI/NIAID NIH HHS/United States
R56 AI127800/AI/NIAID NIH HHS/United States
Journal Article
Netherlands
2019/05/28
EBioMedicine. 2019 Jun;44:112-125. doi: 10.1016/j.ebiom.2019.05.036. Epub 2019 May 23.},
abstract = {BACKGROUND: 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.},
keywords = {Animals
*Catheter Ablation/methods
*Cell Death
Computational Biology/methods
Disease Models, Animal
Disease Progression
*Electroporation/methods
Female
Gene Expression Profiling
Gene Regulatory Networks
Humans
Immune System
*Immunomodulation
Mice
Neoplasms/*immunology/metabolism/pathology/therapy
Signal Transduction
Tumor Microenvironment/immunology
Xenograft Model Antitumor Assays
Breast cancer
Ire
Metastasis
Pyroptosis
Tumor microenvironment},
ISSN = {2352-3964},
DOI = {10.1016/j.ebiom.2019.05.036},
year = {2019},
type = {Journal Article}
}
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Epub 2019 May 23.","abstract":"BACKGROUND: 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. 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H., Jr. and Oestreich, K. J. and Davalos, R. V. and Allen, I. C.},\n title = {High-frequency irreversible electroporation is an effective tumor ablation strategy that induces immunologic cell death and promotes systemic anti-tumor immunity},\n journal = {EBioMedicine},\n volume = {44},\n pages = {112-125},\n note = {2352-3964\nRingel-Scaia, Veronica M\nBeitel-White, Natalie\nLorenzo, Melvin F\nBrock, Rebecca M\nHuie, Kathleen E\nCoutermarsh-Ott, Sheryl\nEden, Kristin\nMcDaniel, Dylan K\nVerbridge, Scott S\nRossmeisl, John H Jr\nOestreich, Kenneth J\nDavalos, Rafael V\nAllen, Irving C\nR01 AI134972/AI/NIAID NIH HHS/United States\nR56 AI127800/AI/NIAID NIH HHS/United States\nJournal Article\nNetherlands\n2019/05/28\nEBioMedicine. 2019 Jun;44:112-125. doi: 10.1016/j.ebiom.2019.05.036. Epub 2019 May 23.},\n abstract = {BACKGROUND: 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. 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