Ionizing radiation modulates human macrophages towards a pro-inflammatory phenotype preserving their pro-invasive and pro-angiogenic capacities

Ana Teresa Pinto, Marta Laranjeiro Pinto, Ana Patrícia Cardoso, Cátia Monteiro, Marta Teixeira Pinto, André Filipe Maia, Patrícia Castro, Rita Figueira, Armanda Monteiro, Margarida Marques, Marc Mareel, Susana Gomes Dos Santos, Raquel Seruca, Mário Adolfo Barbosa, Sónia Rocha, Maria JoséOliveira

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Abstract

In order to improve the efficacy of conventional radiotherapy, attention has been paid to immune cells, which not only modulate cancer cell response to therapy but are also highly recruited to tumours after irradiation. Particularly, the effect of ionizing radiation on macrophages, using therapeutically relevant doses, is not well understood. To evaluate how radiotherapy affects macrophage behaviour and macrophage-mediated cancer cell activity, human monocyte derived-macrophages were subjected, for a week, to cumulative ionizing radiation doses, as used during cancer treatment (2 Gy/fraction/day). Irradiated macrophages remained viable and metabolically active, despite DNA damage. NF-kappaB transcription activation and increased Bcl-xL expression evidenced the promotion of pro-survival activity. A significant increase of pro-inflammatory macrophage markers CD80, CD86 and HLA-DR, but not CCR7, TNF and IL1B was observed after 10 Gy cumulative doses, while anti-inflammatory markers CD163, MRC1, VCAN and IL-10 expression decreased, suggesting the modulation towards a more pro-inflammatory phenotype. Moreover, ionizing radiation induced macrophage morphological alterations and increased their phagocytic rate, without affecting matrix metalloproteases (MMP)2 and MMP9 activity. Importantly, irradiated macrophages promoted cancer cell-invasion and cancer cell-induced angiogenesis. Our work highlights macrophage ability to sustain cancer cell activities as a major concern that needs to be addressed to improve radiotherapy efficacy.

Original languageEnglish
Article number18765
JournalScientific Reports
Volume6
Early online date6 Jan 2016
DOIs
Publication statusPublished - 6 Jan 2016

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  • Cite this

    Teresa Pinto, A., Laranjeiro Pinto, M., Patrícia Cardoso, A., Monteiro, C., Teixeira Pinto, M., Filipe Maia, A., Castro, P., Figueira, R., Monteiro, A., Marques, M., Mareel, M., Dos Santos, S. G., Seruca, R., Adolfo Barbosa, M., Rocha, S., & JoséOliveira, M. (2016). Ionizing radiation modulates human macrophages towards a pro-inflammatory phenotype preserving their pro-invasive and pro-angiogenic capacities. Scientific Reports, 6, [18765]. https://doi.org/10.1038/srep18765