Aneuploid senescent cells activate NF-κB to promote their immune clearance by NK cells
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 fou...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Wang, Ruoxi W [verfasserIn] Viganò, Sonia [verfasserIn] Ben-David, Uri [verfasserIn] Amon, Angelika [verfasserIn] Santaguida, Stefano [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2021 |
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| Schlagwörter: |
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| Anmerkung: |
© The Author(s) 2021 |
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| Übergeordnetes Werk: |
Enthalten in: EMBO Reports - Nature Publishing Group UK, 2023, 22(2021), 8 vom: 08. Juni |
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| Übergeordnetes Werk: |
volume:22 ; year:2021 ; number:8 ; day:08 ; month:06 |
| Links: |
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| DOI / URN: |
10.15252/embr.202052032 |
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| Katalog-ID: |
SPR058026991 |
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| 520 | |a 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. | ||
| 520 | |a SYNOPSIS This study shows that aneuploid cells upregulate NF-κB pathway. This is crucial for promoting an inflammatory state, which in turn leads to NK cell-mediated clearance of aneuploid senescent cells. Natural killer cells engage with and clear aneuploid senescent cells with complex karyotypes.Aneuploidy-induced senescence contributes to cellular cytotoxicity by natural killer cells.NF-κB signaling is central for natural killer cell-mediated clearance of aneuploid senescent cells. | ||
| 520 | |a Graphical Abstract This study shows that aneuploid cells upregulate NF-κB pathway. This is crucial for promoting an inflammatory state, which in turn leads to NK cell-mediated clearance of aneuploid senescent cells. | ||
| 650 | 4 | |a aneuploidy |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a complex karyotypes |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a immune clearance |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a NF-κB |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a senescence |7 (dpeaa)DE-He213 | |
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| 700 | 1 | |a Amon, Angelika |e verfasserin |4 aut | |
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10.15252/embr.202052032 doi (DE-627)SPR058026991 (SPR)embr.202052032-e DE-627 ger DE-627 rakwb eng Wang, Ruoxi W verfasserin aut Aneuploid senescent cells activate NF-κB to promote their immune clearance by NK cells 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 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. SYNOPSIS This study shows that aneuploid cells upregulate NF-κB pathway. This is crucial for promoting an inflammatory state, which in turn leads to NK cell-mediated clearance of aneuploid senescent cells. Natural killer cells engage with and clear aneuploid senescent cells with complex karyotypes.Aneuploidy-induced senescence contributes to cellular cytotoxicity by natural killer cells.NF-κB signaling is central for natural killer cell-mediated clearance of aneuploid senescent cells. Graphical Abstract This study shows that aneuploid cells upregulate NF-κB pathway. This is crucial for promoting an inflammatory state, which in turn leads to NK cell-mediated clearance of aneuploid senescent cells. aneuploidy (dpeaa)DE-He213 complex karyotypes (dpeaa)DE-He213 immune clearance (dpeaa)DE-He213 NF-κB (dpeaa)DE-He213 senescence (dpeaa)DE-He213 Viganò, Sonia verfasserin (orcid)0000-0003-0437-0087 aut Ben-David, Uri verfasserin (orcid)0000-0001-7098-2378 aut Amon, Angelika verfasserin aut Santaguida, Stefano verfasserin (orcid)0000-0002-1501-6190 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 22(2021), 8 vom: 08. Juni (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:22 year:2021 number:8 day:08 month:06 https://dx.doi.org/10.15252/embr.202052032 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 22 2021 8 08 06 |
| spelling |
10.15252/embr.202052032 doi (DE-627)SPR058026991 (SPR)embr.202052032-e DE-627 ger DE-627 rakwb eng Wang, Ruoxi W verfasserin aut Aneuploid senescent cells activate NF-κB to promote their immune clearance by NK cells 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 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. SYNOPSIS This study shows that aneuploid cells upregulate NF-κB pathway. This is crucial for promoting an inflammatory state, which in turn leads to NK cell-mediated clearance of aneuploid senescent cells. Natural killer cells engage with and clear aneuploid senescent cells with complex karyotypes.Aneuploidy-induced senescence contributes to cellular cytotoxicity by natural killer cells.NF-κB signaling is central for natural killer cell-mediated clearance of aneuploid senescent cells. Graphical Abstract This study shows that aneuploid cells upregulate NF-κB pathway. This is crucial for promoting an inflammatory state, which in turn leads to NK cell-mediated clearance of aneuploid senescent cells. aneuploidy (dpeaa)DE-He213 complex karyotypes (dpeaa)DE-He213 immune clearance (dpeaa)DE-He213 NF-κB (dpeaa)DE-He213 senescence (dpeaa)DE-He213 Viganò, Sonia verfasserin (orcid)0000-0003-0437-0087 aut Ben-David, Uri verfasserin (orcid)0000-0001-7098-2378 aut Amon, Angelika verfasserin aut Santaguida, Stefano verfasserin (orcid)0000-0002-1501-6190 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 22(2021), 8 vom: 08. Juni (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:22 year:2021 number:8 day:08 month:06 https://dx.doi.org/10.15252/embr.202052032 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 22 2021 8 08 06 |
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10.15252/embr.202052032 doi (DE-627)SPR058026991 (SPR)embr.202052032-e DE-627 ger DE-627 rakwb eng Wang, Ruoxi W verfasserin aut Aneuploid senescent cells activate NF-κB to promote their immune clearance by NK cells 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 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. SYNOPSIS This study shows that aneuploid cells upregulate NF-κB pathway. This is crucial for promoting an inflammatory state, which in turn leads to NK cell-mediated clearance of aneuploid senescent cells. Natural killer cells engage with and clear aneuploid senescent cells with complex karyotypes.Aneuploidy-induced senescence contributes to cellular cytotoxicity by natural killer cells.NF-κB signaling is central for natural killer cell-mediated clearance of aneuploid senescent cells. Graphical Abstract This study shows that aneuploid cells upregulate NF-κB pathway. This is crucial for promoting an inflammatory state, which in turn leads to NK cell-mediated clearance of aneuploid senescent cells. aneuploidy (dpeaa)DE-He213 complex karyotypes (dpeaa)DE-He213 immune clearance (dpeaa)DE-He213 NF-κB (dpeaa)DE-He213 senescence (dpeaa)DE-He213 Viganò, Sonia verfasserin (orcid)0000-0003-0437-0087 aut Ben-David, Uri verfasserin (orcid)0000-0001-7098-2378 aut Amon, Angelika verfasserin aut Santaguida, Stefano verfasserin (orcid)0000-0002-1501-6190 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 22(2021), 8 vom: 08. Juni (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:22 year:2021 number:8 day:08 month:06 https://dx.doi.org/10.15252/embr.202052032 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 22 2021 8 08 06 |
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10.15252/embr.202052032 doi (DE-627)SPR058026991 (SPR)embr.202052032-e DE-627 ger DE-627 rakwb eng Wang, Ruoxi W verfasserin aut Aneuploid senescent cells activate NF-κB to promote their immune clearance by NK cells 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 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. SYNOPSIS This study shows that aneuploid cells upregulate NF-κB pathway. This is crucial for promoting an inflammatory state, which in turn leads to NK cell-mediated clearance of aneuploid senescent cells. Natural killer cells engage with and clear aneuploid senescent cells with complex karyotypes.Aneuploidy-induced senescence contributes to cellular cytotoxicity by natural killer cells.NF-κB signaling is central for natural killer cell-mediated clearance of aneuploid senescent cells. Graphical Abstract This study shows that aneuploid cells upregulate NF-κB pathway. This is crucial for promoting an inflammatory state, which in turn leads to NK cell-mediated clearance of aneuploid senescent cells. aneuploidy (dpeaa)DE-He213 complex karyotypes (dpeaa)DE-He213 immune clearance (dpeaa)DE-He213 NF-κB (dpeaa)DE-He213 senescence (dpeaa)DE-He213 Viganò, Sonia verfasserin (orcid)0000-0003-0437-0087 aut Ben-David, Uri verfasserin (orcid)0000-0001-7098-2378 aut Amon, Angelika verfasserin aut Santaguida, Stefano verfasserin (orcid)0000-0002-1501-6190 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 22(2021), 8 vom: 08. Juni (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:22 year:2021 number:8 day:08 month:06 https://dx.doi.org/10.15252/embr.202052032 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 22 2021 8 08 06 |
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10.15252/embr.202052032 doi (DE-627)SPR058026991 (SPR)embr.202052032-e DE-627 ger DE-627 rakwb eng Wang, Ruoxi W verfasserin aut Aneuploid senescent cells activate NF-κB to promote their immune clearance by NK cells 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 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. SYNOPSIS This study shows that aneuploid cells upregulate NF-κB pathway. This is crucial for promoting an inflammatory state, which in turn leads to NK cell-mediated clearance of aneuploid senescent cells. Natural killer cells engage with and clear aneuploid senescent cells with complex karyotypes.Aneuploidy-induced senescence contributes to cellular cytotoxicity by natural killer cells.NF-κB signaling is central for natural killer cell-mediated clearance of aneuploid senescent cells. Graphical Abstract This study shows that aneuploid cells upregulate NF-κB pathway. This is crucial for promoting an inflammatory state, which in turn leads to NK cell-mediated clearance of aneuploid senescent cells. aneuploidy (dpeaa)DE-He213 complex karyotypes (dpeaa)DE-He213 immune clearance (dpeaa)DE-He213 NF-κB (dpeaa)DE-He213 senescence (dpeaa)DE-He213 Viganò, Sonia verfasserin (orcid)0000-0003-0437-0087 aut Ben-David, Uri verfasserin (orcid)0000-0001-7098-2378 aut Amon, Angelika verfasserin aut Santaguida, Stefano verfasserin (orcid)0000-0002-1501-6190 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 22(2021), 8 vom: 08. Juni (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:22 year:2021 number:8 day:08 month:06 https://dx.doi.org/10.15252/embr.202052032 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 22 2021 8 08 06 |
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Wang, Ruoxi W @@aut@@ Viganò, Sonia @@aut@@ Ben-David, Uri @@aut@@ Amon, Angelika @@aut@@ Santaguida, Stefano @@aut@@ |
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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 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.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">SYNOPSIS This study shows that aneuploid cells upregulate NF-κB pathway. This is crucial for promoting an inflammatory state, which in turn leads to NK cell-mediated clearance of aneuploid senescent cells. Natural killer cells engage with and clear aneuploid senescent cells with complex karyotypes.Aneuploidy-induced senescence contributes to cellular cytotoxicity by natural killer cells.NF-κB signaling is central for natural killer cell-mediated clearance of aneuploid senescent cells.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Graphical Abstract This study shows that aneuploid cells upregulate NF-κB pathway. 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|
| author |
Wang, Ruoxi W |
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Wang, Ruoxi W misc aneuploidy misc complex karyotypes misc immune clearance misc NF-κB misc senescence Aneuploid senescent cells activate NF-κB to promote their immune clearance by NK cells |
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1469-3178 |
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Aneuploid senescent cells activate NF-κB to promote their immune clearance by NK cells aneuploidy (dpeaa)DE-He213 complex karyotypes (dpeaa)DE-He213 immune clearance (dpeaa)DE-He213 NF-κB (dpeaa)DE-He213 senescence (dpeaa)DE-He213 |
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misc aneuploidy misc complex karyotypes misc immune clearance misc NF-κB misc senescence |
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misc aneuploidy misc complex karyotypes misc immune clearance misc NF-κB misc senescence |
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Aneuploid senescent cells activate NF-κB to promote their immune clearance by NK cells |
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Aneuploid senescent cells activate NF-κB to promote their immune clearance by NK cells |
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Wang, Ruoxi W |
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EMBO Reports |
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Wang, Ruoxi W Viganò, Sonia Ben-David, Uri Amon, Angelika Santaguida, Stefano |
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Elektronische Aufsätze |
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Wang, Ruoxi W |
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10.15252/embr.202052032 |
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aneuploid senescent cells activate nf-κb to promote their immune clearance by nk cells |
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Aneuploid senescent cells activate NF-κB to promote their immune clearance by NK cells |
| abstract |
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. SYNOPSIS This study shows that aneuploid cells upregulate NF-κB pathway. This is crucial for promoting an inflammatory state, which in turn leads to NK cell-mediated clearance of aneuploid senescent cells. Natural killer cells engage with and clear aneuploid senescent cells with complex karyotypes.Aneuploidy-induced senescence contributes to cellular cytotoxicity by natural killer cells.NF-κB signaling is central for natural killer cell-mediated clearance of aneuploid senescent cells. Graphical Abstract This study shows that aneuploid cells upregulate NF-κB pathway. This is crucial for promoting an inflammatory state, which in turn leads to NK cell-mediated clearance of aneuploid senescent cells. © The Author(s) 2021 |
| abstractGer |
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. SYNOPSIS This study shows that aneuploid cells upregulate NF-κB pathway. This is crucial for promoting an inflammatory state, which in turn leads to NK cell-mediated clearance of aneuploid senescent cells. Natural killer cells engage with and clear aneuploid senescent cells with complex karyotypes.Aneuploidy-induced senescence contributes to cellular cytotoxicity by natural killer cells.NF-κB signaling is central for natural killer cell-mediated clearance of aneuploid senescent cells. Graphical Abstract This study shows that aneuploid cells upregulate NF-κB pathway. This is crucial for promoting an inflammatory state, which in turn leads to NK cell-mediated clearance of aneuploid senescent cells. © The Author(s) 2021 |
| abstract_unstemmed |
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. SYNOPSIS This study shows that aneuploid cells upregulate NF-κB pathway. This is crucial for promoting an inflammatory state, which in turn leads to NK cell-mediated clearance of aneuploid senescent cells. Natural killer cells engage with and clear aneuploid senescent cells with complex karyotypes.Aneuploidy-induced senescence contributes to cellular cytotoxicity by natural killer cells.NF-κB signaling is central for natural killer cell-mediated clearance of aneuploid senescent cells. Graphical Abstract This study shows that aneuploid cells upregulate NF-κB pathway. This is crucial for promoting an inflammatory state, which in turn leads to NK cell-mediated clearance of aneuploid senescent cells. © The Author(s) 2021 |
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| title_short |
Aneuploid senescent cells activate NF-κB to promote their immune clearance by NK cells |
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https://dx.doi.org/10.15252/embr.202052032 |
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Viganò, Sonia Ben-David, Uri Amon, Angelika Santaguida, Stefano |
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10.15252/embr.202052032 |
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2024-10-24T04:55:55.738Z |
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| score |
7.4008017 |