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Induced Electric Fields Inhibit Breast Cancer Growth and Metastasis and Modulate the Immune Tumor Microenvironment
Manish Charan1, Travis H Jones2, Dinesh K Ahirwar1,3
1Department of Pathology, College of Medicine, The Ohio State University, Columbus, OH, USA.
Introduction:
Metastatic triple-negative breast cancer (TNBC) remains highly challenging to treat despite advances in oncology. This study investigated whether non-invasive alternating, low-intensity induced electric fields (iEFs) could suppress tumor growth and metastasis while modulating anti-tumor immunity in TNBC.
Methods:
Orthotopic TNBC mouse models were treated with alternating (100 kHz) and low-intensity (2.7 mV/cm peak), induced electric fields (iEFs), which were delivered non-invasively via a solenoid coil system. Tumor growth and lung metastasis were assessed following treatment. Immune profiling was performed to evaluate changes in T cell states and myeloid cell populations within both primary tumors and metastatic lung tissue.
Results:
iEF treatment significantly reduced primary tumor growth (n=9) and lung metastases (n=5). Within the tumor microenvironment, iEFs decreased infiltration of immunosuppressive myeloid cells (n=8). In the lung metastatic niche, iEF therapy increased CD8+ T cell abundance while reducing immunosuppressive myeloid populations (n=8). We also observed that iEFs reduced the metastatic potential of cancer cells by inhibiting epithelial-to-mesenchymal transition (n=3).
Conclusion:
Induced electric field therapy enhances anti-tumor immunity and suppresses metastatic progression in TNBC by enhancing T cell activity and remodeling immunosuppressive myeloid environments. These findings support iEFs as a promising non-invasive immunomodulatory strategy for metastatic TNBC.
Insights
Non-invasive induced electric fields (iEFs) show promise for treating metastatic triple-negative breast cancer (TNBC). This therapy suppresses tumor growth and metastasis by enhancing anti-tumor immunity and reducing immunosuppressive cells.
Area of Science:
- Oncology
- Immunotherapy
- Biophysics
Background:
- Metastatic triple-negative breast cancer (TNBC) presents significant treatment challenges.
- Current therapeutic strategies for TNBC have limitations, necessitating novel approaches.
Purpose of the Study:
- To investigate the efficacy of non-invasive alternating, low-intensity induced electric fields (iEFs) in suppressing TNBC growth and metastasis.
- To evaluate the immunomodulatory effects of iEFs on the tumor microenvironment and metastatic sites.
Main Methods:
- Orthotopic TNBC mouse models were treated with non-invasive iEFs (100 kHz, 2.7 mV/cm peak) using a solenoid coil system.
- Tumor growth, lung metastasis, and immune cell profiling (T cells, myeloid cells) were assessed.
- Epithelial-to-mesenchymal transition (EMT) was evaluated to assess metastatic potential.
Main Results:
- iEF treatment significantly reduced primary tumor growth and lung metastases.
- iEFs decreased immunosuppressive myeloid cell infiltration in primary tumors.
- In lung metastases, iEFs increased CD8+ T cell abundance and reduced immunosuppressive myeloid populations.
- iEFs inhibited EMT, reducing cancer cell metastatic potential.
Conclusions:
- Induced electric field therapy enhances anti-tumor immunity in TNBC.
- iEFs suppress metastatic progression by modulating T cell activity and myeloid cell populations.
- Non-invasive iEFs represent a promising immunomodulatory strategy for metastatic TNBC.
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