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Identifying and characterizing the pathways mediating this immune surveillance are thus critical for understanding how cancer cells are recognized and eliminated. Aneuploidy is a hallmark of cancer, and we previously found that untransformed cells that had undergone senescence due to highly abnormal karyotypes are eliminated by natural killer (NK) cells\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    . However, the mechanisms underlying this process remained elusive. Here, using an\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    NK cell killing system, we show that non-cell-autonomous mechanisms in aneuploid cells predominantly mediate their clearance by NK cells. Our data indicate that in untransformed aneuploid cells, NF-\u03baB signaling upregulation is central to elicit this immune\u00a0response. Inactivating NF-\u03baB abolishes NK cell-mediated clearance of untransformed aneuploid cells. In cancer cell lines, NF-\u03baB upregulation also correlates with the degree of aneuploidy. However, such upregulation in cancer cells is not sufficient to trigger NK cell-mediated clearance, suggesting that additional mechanisms might be at play during cancer evolution to counteract NF-\u03baB-mediated immunogenicity.\n                  <\/jats:p>","DOI":"10.15252\/embr.202052032","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T09:14:13Z","timestamp":1623230053000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["Aneuploid senescent cells activate NF-\u03baB to promote their immune clearance by NK cells"],"prefix":"10.1038","volume":"22","author":[{"given":"Ruoxi W","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0437-0087","authenticated-orcid":false,"given":"Sonia","family":"Vigan\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7098-2378","authenticated-orcid":false,"given":"Uri","family":"Ben-David","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelika","family":"Amon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1501-6190","authenticated-orcid":false,"given":"Stefano","family":"Santaguida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,8]]},"reference":[{"key":"BFEMBR202052032_CR1","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/35099560","volume":"413","author":"L Alexopoulou","year":"2001","unstructured":"Alexopoulou L, Holt AC, Medzhitov R, Flavell RA (2001) Recognition of double-stranded RNA and activation of NF-\u03baB by Toll-like receptor 3. 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