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Updated: Feb 8, 2026
08:37
Reprograming Model of Human Monocyte-derived Macrophages for In-vitro Assays
Published on: April 18, 2025
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Proton irradiation orchestrates macrophage reprogramming through NFκB signaling
Géraldine Genard1, Anne-Catherine Wera1, Camille Huart1
1Cellular Biology Research Unit (URBC)-NARILIS, University of Namur, Namur, Belgium.
Cell Death & Disease
|June 29, 2018
Summary
Proton irradiation can reprogram M2 tumor-associated macrophages (TAMs) to an M1 antitumor phenotype, unlike conventional radiotherapy. This reprogramming, mediated by NFκB, offers new strategies for cancer therapy using charged particle beams.
Area of Science:
- Oncology
- Immunology
- Radiation Biology
Background:
- Tumor-associated macrophages (TAMs) often exhibit an M2-like phenotype, promoting tumor progression and treatment resistance.
- Conventional radiotherapy (RT) fails to reprogram TAMs to an M1 antitumor phenotype.
- Proton therapy is an emerging RT modality with potential for improved cancer treatment outcomes.
Purpose of the Study:
- To investigate the effects of proton irradiation on macrophage polarization.
- To determine if proton therapy can reprogram M2 TAMs towards an M1 phenotype.
- To elucidate the molecular mechanisms underlying proton irradiation-induced macrophage reprogramming.
Main Methods:
- Irradiation of M1, M0, and M2 macrophages with protons.
- Assessment of macrophage resistance and DNA damage.
- Analysis of NFκB signaling pathway activation, including IκBα phosphorylation and p65 nuclear translocation.
Main Results:
- M1 macrophages demonstrated greater resistance to proton irradiation compared to M0 and M2 macrophages, linked to differential DNA damage detection.
- Proton irradiation induced reprogramming of M2 macrophages to a mixed M1/M2 phenotype.
- Macrophage reprogramming was dependent on NFκB p65 nuclear translocation, as inhibiting IκBα phosphorylation reversed the effect.
Conclusions:
- Proton irradiation promotes NFκB-mediated polarization of macrophages towards an M1 phenotype.
- Charged particle therapy offers novel perspectives for targeting macrophages in cancer treatment.
- Proton therapy may overcome limitations of conventional RT in modulating the tumor immune microenvironment.
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