M2 macrophages are more resistant than M1 macrophages following radiation therapy in the context of glioblastoma
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Marine M. Leblond1, Elodie A. Pérès1, Charly Helaine1, Aurélie N. Gérault1, Damien Moulin1, Clément Anfray1, Didier Divoux1, Edwige Petit1, Myriam Bernaudin1 and Samuel Valable1
1Normandie Université, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, 14000 Caen, France
Samuel Valable, email: [email protected]
Keywords: macrophages, irradiation, glioblastoma, radioresistance, phenotypic selection
Received: December 21, 2016 Accepted: July 23, 2017 Published: August 07, 2017
In some highly inflammatory tumors, such as glioblastoma (GB), macrophages (MΦ) represent the most abundant population of reactive cells. MΦ, initially denoted as M0 MΦ, can be polarized into two further phenotypes: the antitumor M1 MΦ, and the protumor M2 MΦ. The three phenotypes can reside simultaneously in the tumor mass and various external factors may influence MΦ 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 MΦ present in GB tumors. We have observed a decrease in MΦ number paralleled by an increase in the proportion of M2 MΦ. To understand this phenomenon, we then evaluated, in vitro, the effects of X-rays on the MΦ phenotypes and survival. We have found that X-ray radiation failed to modify the phenotype of the different MΦ. However, M1 MΦ were more sensitive to ionizing radiation than M2 MΦ, both in normoxia and in hypoxia, which could explain the in vivo observations. To conclude, M2 MΦ are more radioresistant than M0 and M1 MΦ 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 MΦ in GB.
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