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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\u2009Gy\/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<jats:italic>CD80<\/jats:italic>, CD86 and HLA-DR, but not<jats:italic>CCR7<\/jats:italic>,<jats:italic>TNF<\/jats:italic>and<jats:italic>IL1B<\/jats:italic>was observed after 10\u2009Gy cumulative doses, while anti-inflammatory markers<jats:italic>CD163<\/jats:italic>,<jats:italic>MRC1<\/jats:italic>,<jats:italic>VCAN<\/jats:italic>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.<\/jats:p>","DOI":"10.1038\/srep18765","type":"journal-article","created":{"date-parts":[[2016,1,6]],"date-time":"2016-01-06T14:26:57Z","timestamp":1452090417000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":173,"title":["Ionizing radiation modulates human macrophages towards a pro-inflammatory phenotype preserving their pro-invasive and pro-angiogenic capacities"],"prefix":"10.1038","volume":"6","author":[{"given":"Ana","family":"Teresa Pinto","sequence":"first","affiliation":[]},{"given":"Marta","family":"Laranjeiro Pinto","sequence":"additional","affiliation":[]},{"given":"Ana","family":"Patr\u00edcia Cardoso","sequence":"additional","affiliation":[]},{"given":"C\u00e1tia","family":"Monteiro","sequence":"additional","affiliation":[]},{"given":"Marta","family":"Teixeira Pinto","sequence":"additional","affiliation":[]},{"given":"Andr\u00e9","family":"Filipe Maia","sequence":"additional","affiliation":[]},{"given":"Patr\u00edcia","family":"Castro","sequence":"additional","affiliation":[]},{"given":"Rita","family":"Figueira","sequence":"additional","affiliation":[]},{"given":"Armanda","family":"Monteiro","sequence":"additional","affiliation":[]},{"given":"Margarida","family":"Marques","sequence":"additional","affiliation":[]},{"given":"Marc","family":"Mareel","sequence":"additional","affiliation":[]},{"given":"Susana Gomes","family":"dos Santos","sequence":"additional","affiliation":[]},{"given":"Raquel","family":"Seruca","sequence":"additional","affiliation":[]},{"given":"M\u00e1rio","family":"Adolfo Barbosa","sequence":"additional","affiliation":[]},{"given":"S\u00f3nia","family":"Rocha","sequence":"additional","affiliation":[]},{"given":"Maria","family":"Jos\u00e9 Oliveira","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2016,1,6]]},"reference":[{"key":"BFsrep18765_CR1","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1002\/cncr.21324","volume":"104","author":"G Delaney","year":"2005","unstructured":"Delaney, G., Jacob, S., Featherstone, C. & Barton, M. 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