Nanopulse Stimulation (NPS) Induces Tumor Ablation and Immunity in Orthotopic 4T1 Mouse Breast Cancer: A Review
Nanopulse Stimulation (NPS) eliminates mouse and rat tumor types in several different animal models. NPS induces protective, vaccine-like effects after ablation of orthotopic rat N1-S1 hepatocellular carcinoma. Here we review some general concepts of NPS in the context of studies with mouse metastat...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-03-01
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| Series: | Cancers |
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| Online Access: | http://www.mdpi.com/2072-6694/10/4/97 |
| _version_ | 1797762707050463232 |
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| author | Stephen J. Beebe Brittany P. Lassiter Siqi Guo |
| author_facet | Stephen J. Beebe Brittany P. Lassiter Siqi Guo |
| author_sort | Stephen J. Beebe |
| collection | DOAJ |
| description | Nanopulse Stimulation (NPS) eliminates mouse and rat tumor types in several different animal models. NPS induces protective, vaccine-like effects after ablation of orthotopic rat N1-S1 hepatocellular carcinoma. Here we review some general concepts of NPS in the context of studies with mouse metastatic 4T1 mammary cancer showing that the postablation, vaccine-like effect is initiated by dynamic, multilayered immune mechanisms. NPS eliminates primary 4T1 tumors by inducing immunogenic, caspase-independent programmed cell death (PCD). With lower electric fields, like those peripheral to the primary treatment zone, NPS can activate dendritic cells (DCs). The activation of DCs by dead/dying cells leads to increases in memory effector and central memory T-lymphocytes in the blood and spleen. NPS also eliminates immunosuppressive cells in the tumor microenvironment and blood. Finally, NPS treatment of 4T1 breast cancer exhibits an abscopal effect and largely prevents spontaneous metastases to distant organs. NPS with fast rise–fall times and pulse durations near the plasma membrane charging time constant, which exhibits transient, high-frequency components (1/time = Hz), induce responses from mitochondria, endoplasmic reticulum, and nucleus. Such effects may be responsible for release of danger-associated molecular patterns, including ATP, calreticulin, and high mobility group box 1 (HMBG1) from 4T1-Luc cells to induce immunogenic cell death (ICD). This likely leads to immunity and the vaccine-like response. In this way, NPS acts as a unique onco-immunotherapy providing distinct therapeutic advantages showing possible clinical utility for breast cancers as well as for other malignancies. |
| first_indexed | 2024-03-12T19:31:17Z |
| format | Article |
| id | doaj.art-1f49101586dd47bab3e0f215922c46b3 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T19:31:17Z |
| publishDate | 2018-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-1f49101586dd47bab3e0f215922c46b32023-08-02T04:29:07ZengMDPI AGCancers2072-66942018-03-011049710.3390/cancers10040097cancers10040097Nanopulse Stimulation (NPS) Induces Tumor Ablation and Immunity in Orthotopic 4T1 Mouse Breast Cancer: A ReviewStephen J. Beebe0Brittany P. Lassiter1Siqi Guo2Frank Reidy Research Center for Bioelectrics, 4211 Monarch Ways, Suite 300, Norfolk, VA 23508, USAFrank Reidy Research Center for Bioelectrics, 4211 Monarch Ways, Suite 300, Norfolk, VA 23508, USAFrank Reidy Research Center for Bioelectrics, 4211 Monarch Ways, Suite 300, Norfolk, VA 23508, USANanopulse Stimulation (NPS) eliminates mouse and rat tumor types in several different animal models. NPS induces protective, vaccine-like effects after ablation of orthotopic rat N1-S1 hepatocellular carcinoma. Here we review some general concepts of NPS in the context of studies with mouse metastatic 4T1 mammary cancer showing that the postablation, vaccine-like effect is initiated by dynamic, multilayered immune mechanisms. NPS eliminates primary 4T1 tumors by inducing immunogenic, caspase-independent programmed cell death (PCD). With lower electric fields, like those peripheral to the primary treatment zone, NPS can activate dendritic cells (DCs). The activation of DCs by dead/dying cells leads to increases in memory effector and central memory T-lymphocytes in the blood and spleen. NPS also eliminates immunosuppressive cells in the tumor microenvironment and blood. Finally, NPS treatment of 4T1 breast cancer exhibits an abscopal effect and largely prevents spontaneous metastases to distant organs. NPS with fast rise–fall times and pulse durations near the plasma membrane charging time constant, which exhibits transient, high-frequency components (1/time = Hz), induce responses from mitochondria, endoplasmic reticulum, and nucleus. Such effects may be responsible for release of danger-associated molecular patterns, including ATP, calreticulin, and high mobility group box 1 (HMBG1) from 4T1-Luc cells to induce immunogenic cell death (ICD). This likely leads to immunity and the vaccine-like response. In this way, NPS acts as a unique onco-immunotherapy providing distinct therapeutic advantages showing possible clinical utility for breast cancers as well as for other malignancies.http://www.mdpi.com/2072-6694/10/4/97programmed cell deathimmunogenic cell deathimmunosuppressiontumor microenvironmentdanger-associated molecular patternsplasma membrane charging time constant (3–10) |
| spellingShingle | Stephen J. Beebe Brittany P. Lassiter Siqi Guo Nanopulse Stimulation (NPS) Induces Tumor Ablation and Immunity in Orthotopic 4T1 Mouse Breast Cancer: A Review Cancers programmed cell death immunogenic cell death immunosuppression tumor microenvironment danger-associated molecular patterns plasma membrane charging time constant (3–10) |
| title | Nanopulse Stimulation (NPS) Induces Tumor Ablation and Immunity in Orthotopic 4T1 Mouse Breast Cancer: A Review |
| title_full | Nanopulse Stimulation (NPS) Induces Tumor Ablation and Immunity in Orthotopic 4T1 Mouse Breast Cancer: A Review |
| title_fullStr | Nanopulse Stimulation (NPS) Induces Tumor Ablation and Immunity in Orthotopic 4T1 Mouse Breast Cancer: A Review |
| title_full_unstemmed | Nanopulse Stimulation (NPS) Induces Tumor Ablation and Immunity in Orthotopic 4T1 Mouse Breast Cancer: A Review |
| title_short | Nanopulse Stimulation (NPS) Induces Tumor Ablation and Immunity in Orthotopic 4T1 Mouse Breast Cancer: A Review |
| title_sort | nanopulse stimulation nps induces tumor ablation and immunity in orthotopic 4t1 mouse breast cancer a review |
| topic | programmed cell death immunogenic cell death immunosuppression tumor microenvironment danger-associated molecular patterns plasma membrane charging time constant (3–10) |
| url | http://www.mdpi.com/2072-6694/10/4/97 |
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