Aneuploid senescent cells activate NF-κB to promote their immune clearance by NK cells
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44319_2021_Article_BFEMBR202052032.pdf
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Author(s)
Wang, Ruoxi W.
Viganò, Sonia
Ben-David, Uri
Amon, Angelika
Santaguida, Stefano
Date Issued
June 8, 2021
Journal
Embo Reports
Publisher
Nature Publishing Group UK
Citation
The EMBO Reports. 2021 Jun 08;22(8):EMBR202052032
Version
Final published version
Abstract
The immune system plays a major role in the protection against cancer. 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 in vitro. However, the mechanisms underlying this process remained elusive. Here, using an in vitro 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‐κB signaling upregulation is central to elicit this immune response. Inactivating NF‐κB abolishes NK cell‐mediated clearance of untransformed aneuploid cells. In cancer cell lines, NF‐κB 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‐κB‐mediated immunogenicity.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Howard Hughes Medical Institute
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.15252/embr.202052032
