Journal
ONCOTARGET
Volume 8, Issue 42, Pages 72597-72612Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.19994
Keywords
macrophages; irradiation; glioblastoma; radioresistance; phenotypic selection
Categories
Funding
- Centre National de la Recherche Scientifique (CNRS)
- Universite de Caen-Normandie (UNICAEN)
- French Ministere de l'Enseignement Superieur et de la Recherche (MESR)
- Conseil Regional de Basse-Normandie (CRBN)
- Advanced Resource Center for Hadrontherapy in Europe (Archade)
- Federation pour la Recherche sur le Cerveau par l'operation Rotary Espoir en tete >> (FRC)
- French National Agency for Research [ANR-11-LABEX-0018-01, ANR-10-EQPX-1401, ANR-11-INSB-0007]
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In some highly inflammatory tumors, such as glioblastoma (GB), macrophages (M Phi) represent the most abundant population of reactive cells. M Phi, initially denoted as M0 M Phi, can be polarized into two further phenotypes: the antitumor M1 M Phi, and the protumor M2 M Phi. The three phenotypes can reside simultaneously in the tumor mass and various external factors may influence M Phi polarization. Radiotherapy is a common modality of cancer treatment aiming to target tumor cells. However, the specific effects of X-ray radiation on the inflammatory cells are, so far, controversial and not fully understood. In the present investigation, we have first analyzed, in vivo, the effect of X-ray radiation on M Phi present in GB tumors. We have observed a decrease in M Phi number paralleled by an increase in the proportion of M2 M Phi. To understand this phenomenon, we then evaluated, in vitro, the effects of X-rays on the M Phi phenotypes and survival. We have found that X-ray radiation failed to modify the phenotype of the different M Phi. However, M1 M Phi were more sensitive to ionizing radiation than M2 M Phi, both in normoxia and in hypoxia, which could explain the in vivo observations. To conclude, M2 M Phi are more radioresistant than M0 and M1 M Phi and the present study allows us to propose that X-ray radiotherapy could contribute, along with other phenomena, to the increased density in the protumor M2 M Phi in GB.
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