期刊
EMBO REPORTS
卷 22, 期 8, 页码 -出版社
WILEY
DOI: 10.15252/embr.202052032
关键词
aneuploidy; complex karyotypes; immune clearance; NF-kappa B; senescence
资金
- Italian Association for Cancer Research (MFAG 2018) [21665]
- Fondazione Cariplo, Ricerca Finalizzata [GR-2018-12367077]
- Rita-Levi Montalcini program from MIUR
- Italian Ministry of Health
- NIH [CA206157]
- Azrieli Foundation
- Richard Eimert Research Fund on Solid Tumors
- Tel Aviv University Cancer Biology Research Center
- Israel Cancer Association
The study suggests that non-cell-autonomous mechanisms in aneuploid cells predominantly mediate their clearance by NK cells, with NF-kappa B signaling upregulation playing a central role in triggering the immune response. While NF-kappa B upregulation correlates with the degree of aneuploidy in cancer cell lines, it is not sufficient to trigger NK cell-mediated clearance, indicating that additional mechanisms may be at play during cancer evolution to counteract NF-kappa B-mediated immunogenicity.
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-kappa B signaling upregulation is central to elicit this immune response. Inactivating NF-kappa B abolishes NK cell-mediated clearance of untransformed aneuploid cells. In cancer cell lines, NF-kappa B 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-kappa B-mediated immunogenicity.
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