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Hypoxic inflammatory macrophages are characterized by a cluster of proinflammatory genes undergoing ten-eleven translocation\u2013mediated DNA demethylation and overexpression. These genes are regulated by NF-\u03baB, while HIF1\u03b1 dominates the transcriptional reprogramming, demonstrated through ChIP-seq and pharmacological inhibition. In bladder and ovarian carcinomas, hypoxic inflammatory macrophages are enriched in immune-infiltrated tumors, correlating with better patient prognoses. Coculture assays and cell-cell communication analyses support that hypoxic-activated macrophages enhance T cell\u2013mediated responses. The NF-\u03baB\u2013associated hypomethylation signature is displayed by a subset of hypoxic inflammatory macrophages, isolated from ovarian tumors. Our results challenge paradigms regarding the effects of hypoxia on macrophages and highlight actionable target cells to modulate anticancer immune responses.<\/jats:p>","DOI":"10.1126\/sciadv.adq5226","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T17:59:11Z","timestamp":1726682351000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":48,"title":["NF-\u03baB and TET2 promote macrophage reprogramming in hypoxia that overrides the immunosuppressive effects of the tumor microenvironment"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3026-3069","authenticated-orcid":true,"given":"Carlos","family":"de la Calle-Fabregat","sequence":"first","affiliation":[{"name":"Epigenetics and Immune Disease Group, Josep Carreras Leukaemia Research Institute (IJC), 08916 Badalona, Barcelona, Spain."},{"name":"INSERM UMR1015, Gustave Roussy Cancer Campus, 94805 Villejuif, 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