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.

Abstract

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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