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Updated: Jan 21, 2026

The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma
Published on: April 16, 2019
Tumor-Treating Fields Induce RAW264.7 Macrophage Activation Via NK-κB/MAPK Signaling Pathways
Jeong-In Park1,2, Kyung-Hee Song1, Seung-Youn Jung1
11 Division of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea.
Objective:
Tumor-treating fields are currently used to successfully treat various cancers; however, the specific pathways associated with its efficacy remain unknown in the immune responses. Here, we evaluated tumor-treating fields-mediated initiation of the macrophage-specific immune response.
Materials And Methods:
We subjected RAW 264.7 mouse macrophages to clinically relevant levels of tumor-treating fields (0.9 V/cm, 150 kHz) and evaluated alterations in cytokine expression and release, as well as cell viability. Additionally, we investigated the status of immunomodulatory pathways to determine their roles in tumor-treating fields-mediated immune activation.
Results And Discussion:
Our results indicated that tumor-treating fields treatment at 0.9 V/cm decreased cell viability and increased cytokine messenger RNA/protein levels, as well as levels of nitric oxide and reactive oxygen species, relative to controls. The levels of tumor necrosis factor α, interleukin 1β, and interleukin 6 were markedly increased in tumor-treating fields-treated RAW 264.7 cells cocultured with 4T1 murine mammary carcinoma cells compared with those in 4T1 or RAW 264.7 cells with or without tumor-treating fields treatment. Moreover, the viability of 4T1 cells treated with the conditioned medium of tumor-treating fields-stimulated RAW 264.7 cells decreased, indicating that macrophage activation by tumor-treating fields effectively killed the tumor cells. Moreover, tumor-treating fields treatment activated the nuclear factor κB and mitogen-activated protein kinase pathways involved in immunomodulatory signaling.
Conclusion:
These results provide critical insights into the mechanisms through which tumor-treating fields affect macrophage-specific immune responses and the efficacy of this method for cancer treatment.
Insights
Tumor-treating fields activate macrophages, enhancing immune responses against cancer cells. This study reveals how these fields stimulate macrophages, leading to tumor cell death.
Area of Science:
- Immunology
- Oncology
- Biophysics
Background:
- Tumor-treating fields (TTFields) are an established cancer therapy.
- The precise mechanisms by which TTFields influence the immune system, particularly macrophages, are not fully understood.
Purpose of the Study:
- To investigate the effects of TTFields on macrophage-specific immune responses.
- To elucidate the role of immunomodulatory pathways in TTFields-mediated immune activation.
Main Methods:
- RAW 264.7 mouse macrophages were exposed to clinically relevant TTFields (0.9 V/cm, 150 kHz).
- Assessed changes in cytokine expression, release, nitric oxide, and reactive oxygen species.
- Investigated the activation of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways.
Main Results:
- TTFields treatment reduced macrophage viability and increased cytokine (TNF-α, IL-1β, IL-6), nitric oxide, and reactive oxygen species levels.
- TTFields-stimulated macrophages effectively reduced the viability of cocultured 4T1 murine mammary carcinoma cells.
- TTFields activated NF-κB and MAPK signaling pathways.
Conclusions:
- TTFields modulate macrophage-specific immune responses.
- Macrophage activation by TTFields contributes to tumor cell killing, offering insights into TTFields' cancer treatment efficacy.
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