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

ABSTRACT: In some highly inflammatory tumors, such as glioblastoma (GB), macrophages (M?) represent the most abundant population of reactive cells. M?, initially denoted as M0 M?, can be polarized into two further phenotypes: the antitumor M1 M?, and the protumor M2 M?. The three phenotypes can reside simultaneously in the tumor mass and various external factors may influence M? 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? present in GB tumors. We have observed a decrease in M? number paralleled by an increase in the proportion of M2 M?. To understand this phenomenon, we then evaluated, in vitro, the effects of X-rays on the M? phenotypes and survival. We have found that X-ray radiation failed to modify the phenotype of the different M?. However, M1 M? were more sensitive to ionizing radiation than M2 M?, both in normoxia and in hypoxia, which could explain the in vivo observations. To conclude, M2 M? are more radioresistant than M0 and M1 M? 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? in GB.

SUBMITTER: Leblond MM

PROVIDER: S-EPMC5641155 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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

Leblond Marine M MM Pérès Elodie A EA Helaine Charly C Gérault Aurélie N AN Moulin Damien D Anfray Clément C Divoux Didier D Petit Edwige E Bernaudin Myriam M Valable Samuel S

Oncotarget 20170807 42

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 ...[more]

PMID: 29069812

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Project description:Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th) 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a suitable tool for the characterisation of macrophage polarisation in situ. Furthermore, CD163 cannot be considered a reliable M2 marker when used on its own.

Dataset Information

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

Publications

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

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