{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T17:53:32Z","timestamp":1764784412711,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,3,28]],"date-time":"2020-03-28T00:00:00Z","timestamp":1585353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-031859 (MAGICIAM)"],"award-info":[{"award-number":["POCI-01-0145-FEDER-031859 (MAGICIAM)"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>In colon cancer, the prognostic value of macrophages is controversial, and it is still unknown how hypoxia modulates macrophage\u2013cancer cell crosstalk. To unravel this, co-cultures of human primary macrophages and colon cancer cells were performed at 20% and 1% O2, followed by characterization of both cellular components. Different colon cancer patient cohorts were analyzed for hypoxia and immune markers, and their association with patient overall survival was established. A positive correlation between HIF1A and CD68 in colon cancer patients was identified but, unexpectedly, in cases with higher macrophage infiltration, HIF1A expression was associated with a better prognosis, in contrast to breast, gastric, and lung cancers. Under hypoxia, co-cultures\u2019 secretome indicated a shift towards a pro-inflammatory phenotype. These alterations occurred along with increased macrophage phagocytic activity and decreased SIRP\u03b1 expression. Cancer cells were more invasive and exhibited higher CD47 expression. We hypothesize that the better prognosis associated with HIF1AHighCD68High tumors could occur due to macrophagic pro-inflammatory pressure. Indeed, we found that tumors HIF1AHighCD68High expressed increased levels of CD8A, which is positively correlated with HIF1A. In conclusion, we show that in colon cancer, hypoxia drives macrophages into a pro-inflammatory phenotype, concomitant with increased infiltration of anti-tumor immune cells, favoring better disease outcome.<\/jats:p>","DOI":"10.3390\/cancers12040818","type":"journal-article","created":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T05:52:30Z","timestamp":1585720350000},"page":"818","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Hypoxia and Macrophages Act in Concert Towards a Beneficial Outcome in Colon Cancer"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5773-2881","authenticated-orcid":false,"given":"Fl\u00e1via","family":"Martins","sequence":"first","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"INEB-Institute of Biomedical Engineering, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal"},{"name":"Department of Pathology and Oncology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"given":"Rosa","family":"Oliveira","sequence":"additional","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"INEB-Institute of Biomedical Engineering, University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Bruno","family":"Cavadas","sequence":"additional","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2330-9863","authenticated-orcid":false,"given":"Filipe","family":"Pinto","sequence":"additional","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1987-0316","authenticated-orcid":false,"given":"Ana Patr\u00edcia","family":"Cardoso","sequence":"additional","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"INEB-Institute of Biomedical Engineering, University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2273-2806","authenticated-orcid":false,"given":"Fl\u00e1via","family":"Castro","sequence":"additional","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"INEB-Institute of Biomedical Engineering, University of Porto, 4200-135 Porto, Portugal"},{"name":"ICBAS-Institute of Biomedical Sciences Abel Salazar, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0990-022X","authenticated-orcid":false,"given":"B\u00e1rbara","family":"Sousa","sequence":"additional","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5783-3965","authenticated-orcid":false,"given":"Marta Laranjeiro","family":"Pinto","sequence":"additional","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"INEB-Institute of Biomedical Engineering, University of Porto, 4200-135 Porto, Portugal"},{"name":"CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal"}]},{"given":"Ana Jo\u00e3o","family":"Silva","sequence":"additional","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"INEB-Institute of Biomedical Engineering, University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Diogo","family":"Ad\u00e3o","sequence":"additional","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"INEB-Institute of Biomedical Engineering, University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1744-6135","authenticated-orcid":false,"given":"Jos\u00e9 Pedro","family":"Loureiro","sequence":"additional","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IBMC-Institute of Molecular and Cellular Biology, University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Nicole","family":"Pedro","sequence":"additional","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9639-7940","authenticated-orcid":false,"given":"Rui Manuel","family":"Reis","sequence":"additional","affiliation":[{"name":"Molecular Oncology Research Center, Barretos Cancer Hospital, 14.784-400 Barretos-SP, Brazil"},{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"given":"Lu\u00edsa","family":"Pereira","sequence":"additional","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal"},{"name":"Department of Pathology and Oncology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0724-0272","authenticated-orcid":false,"given":"Maria Jos\u00e9","family":"Oliveira","sequence":"additional","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"INEB-Institute of Biomedical Engineering, University of Porto, 4200-135 Porto, Portugal"},{"name":"Department of Pathology and Oncology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"ICBAS-Institute of Biomedical Sciences Abel Salazar, University 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