M2 macrophages are more resistant than M1 macrophages following radiation therapy in the context of glioblastoma

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.