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Résumé

Tumor-associated macrophages (TAMs) represent potential targets for anticancer treatments as these cells play critical roles in tumor progression and frequently antagonize the response to treatments. TAMs are usually associated to an M2-like phenotype, characterized by anti-inflammatory and protumoral properties. This phenotype contrasts with the M1-like macrophages, which exhibits proinflammatory, phagocytic, and antitumoral functions. As macrophages hold a high plasticity, strategies to orchestrate the reprogramming of M2-like TAMs towards a M1 antitumor phenotype offer potential therapeutic benefits. One of the most used anticancer treatments is the conventional X-ray radiotherapy (RT), but this therapy failed to reprogram TAMs towards an M1 phenotype. While protontherapy is more and more used in clinic to circumvent the side effects of conventional RT, the effects of proton irradiation on macrophages have not been investigated yet. Here we showed that M1 macrophages (THP-1 cell line) were more resistant to proton irradiation than unpolarized (M0) and M2 macrophages, which correlated with differential DNA damage detection. Moreover, proton irradiation-induced macrophage reprogramming from M2 to a mixed M1/M2 phenotype. This reprogramming required the nuclear translocation of NFκB p65 subunit as the inhibition of IκBα phosphorylation completely reverted the macrophage re-education. Altogether, the results suggest that proton irradiation promotes NFκB-mediated macrophage polarization towards M1 and opens new perspectives for macrophage targeting with charged particle therapy.

langue originaleAnglais
Numéro d'article728
Nombre de pages13
journalCell Death and Disease
Volume9
Numéro de publication7
Les DOIs
étatPublié - 2018

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Protons
Macrophages
Phenotype
Neoplasms
Radiotherapy
X-Ray Therapy
Therapeutics
DNA Damage
Anti-Inflammatory Agents
Phosphorylation
Education
Cell Line

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@article{9760ee3dc03b4af6acbc11c01aebe142,
title = "Proton irradiation orchestrates macrophage reprogramming through NFκB signaling",
abstract = "Tumor-associated macrophages (TAMs) represent potential targets for anticancer treatments as these cells play critical roles in tumor progression and frequently antagonize the response to treatments. TAMs are usually associated to an M2-like phenotype, characterized by anti-inflammatory and protumoral properties. This phenotype contrasts with the M1-like macrophages, which exhibits proinflammatory, phagocytic, and antitumoral functions. As macrophages hold a high plasticity, strategies to orchestrate the reprogramming of M2-like TAMs towards a M1 antitumor phenotype offer potential therapeutic benefits. One of the most used anticancer treatments is the conventional X-ray radiotherapy (RT), but this therapy failed to reprogram TAMs towards an M1 phenotype. While protontherapy is more and more used in clinic to circumvent the side effects of conventional RT, the effects of proton irradiation on macrophages have not been investigated yet. Here we showed that M1 macrophages (THP-1 cell line) were more resistant to proton irradiation than unpolarized (M0) and M2 macrophages, which correlated with differential DNA damage detection. Moreover, proton irradiation-induced macrophage reprogramming from M2 to a mixed M1/M2 phenotype. This reprogramming required the nuclear translocation of NFκB p65 subunit as the inhibition of IκBα phosphorylation completely reverted the macrophage re-education. Altogether, the results suggest that proton irradiation promotes NFκB-mediated macrophage polarization towards M1 and opens new perspectives for macrophage targeting with charged particle therapy.",
author = "G{\'e}raldine Genard and Wera, {Anne Catherine} and Camille Huart and {Le Calve}, Benjamin and S{\'e}bastien Penninckx and Antoine Fattaccioli and Tijani Tabarrant and Catherine Demazy and No{\"e}lle Ninane and Heuskin, {Anne Catherine} and St{\'e}phane Lucas and Carine Michiels",
year = "2018",
doi = "10.1038/s41419-018-0757-9",
language = "English",
volume = "9",
journal = "Cell Death and Disease",
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T1 - Proton irradiation orchestrates macrophage reprogramming through NFκB signaling

AU - Genard, Géraldine

AU - Wera, Anne Catherine

AU - Huart, Camille

AU - Le Calve, Benjamin

AU - Penninckx, Sébastien

AU - Fattaccioli, Antoine

AU - Tabarrant, Tijani

AU - Demazy, Catherine

AU - Ninane, Noëlle

AU - Heuskin, Anne Catherine

AU - Lucas, Stéphane

AU - Michiels, Carine

PY - 2018

Y1 - 2018

N2 - Tumor-associated macrophages (TAMs) represent potential targets for anticancer treatments as these cells play critical roles in tumor progression and frequently antagonize the response to treatments. TAMs are usually associated to an M2-like phenotype, characterized by anti-inflammatory and protumoral properties. This phenotype contrasts with the M1-like macrophages, which exhibits proinflammatory, phagocytic, and antitumoral functions. As macrophages hold a high plasticity, strategies to orchestrate the reprogramming of M2-like TAMs towards a M1 antitumor phenotype offer potential therapeutic benefits. One of the most used anticancer treatments is the conventional X-ray radiotherapy (RT), but this therapy failed to reprogram TAMs towards an M1 phenotype. While protontherapy is more and more used in clinic to circumvent the side effects of conventional RT, the effects of proton irradiation on macrophages have not been investigated yet. Here we showed that M1 macrophages (THP-1 cell line) were more resistant to proton irradiation than unpolarized (M0) and M2 macrophages, which correlated with differential DNA damage detection. Moreover, proton irradiation-induced macrophage reprogramming from M2 to a mixed M1/M2 phenotype. This reprogramming required the nuclear translocation of NFκB p65 subunit as the inhibition of IκBα phosphorylation completely reverted the macrophage re-education. Altogether, the results suggest that proton irradiation promotes NFκB-mediated macrophage polarization towards M1 and opens new perspectives for macrophage targeting with charged particle therapy.

AB - Tumor-associated macrophages (TAMs) represent potential targets for anticancer treatments as these cells play critical roles in tumor progression and frequently antagonize the response to treatments. TAMs are usually associated to an M2-like phenotype, characterized by anti-inflammatory and protumoral properties. This phenotype contrasts with the M1-like macrophages, which exhibits proinflammatory, phagocytic, and antitumoral functions. As macrophages hold a high plasticity, strategies to orchestrate the reprogramming of M2-like TAMs towards a M1 antitumor phenotype offer potential therapeutic benefits. One of the most used anticancer treatments is the conventional X-ray radiotherapy (RT), but this therapy failed to reprogram TAMs towards an M1 phenotype. While protontherapy is more and more used in clinic to circumvent the side effects of conventional RT, the effects of proton irradiation on macrophages have not been investigated yet. Here we showed that M1 macrophages (THP-1 cell line) were more resistant to proton irradiation than unpolarized (M0) and M2 macrophages, which correlated with differential DNA damage detection. Moreover, proton irradiation-induced macrophage reprogramming from M2 to a mixed M1/M2 phenotype. This reprogramming required the nuclear translocation of NFκB p65 subunit as the inhibition of IκBα phosphorylation completely reverted the macrophage re-education. Altogether, the results suggest that proton irradiation promotes NFκB-mediated macrophage polarization towards M1 and opens new perspectives for macrophage targeting with charged particle therapy.

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