Cellular Senescence Is Immunogenic and Promotes Antitumor Immunity.
Journal
Cancer discovery
ISSN: 2159-8290
Titre abrégé: Cancer Discov
Pays: United States
ID NLM: 101561693
Informations de publication
Date de publication:
06 02 2023
06 02 2023
Historique:
received:
04
05
2022
revised:
31
08
2022
accepted:
24
10
2022
pubmed:
28
10
2022
medline:
8
2
2023
entrez:
27
10
2022
Statut:
ppublish
Résumé
Cellular senescence is a stress response that activates innate immune cells, but little is known about its interplay with the adaptive immune system. Here, we show that senescent cells combine several features that render them highly efficient in activating dendritic cells (DC) and antigen-specific CD8 T cells. This includes the release of alarmins, activation of IFN signaling, enhanced MHC class I machinery, and presentation of senescence-associated self-peptides that can activate CD8 T cells. In the context of cancer, immunization with senescent cancer cells elicits strong antitumor protection mediated by DCs and CD8 T cells. Interestingly, this protection is superior to immunization with cancer cells undergoing immunogenic cell death. Finally, the induction of senescence in human primary cancer cells also augments their ability to activate autologous antigen-specific tumor-infiltrating CD8 lymphocytes. Our study indicates that senescent cancer cells can be exploited to develop efficient and protective CD8-dependent antitumor immune responses. Our study shows that senescent cells are endowed with a high immunogenic potential-superior to the gold standard of immunogenic cell death. We harness these properties of senescent cells to trigger efficient and protective CD8-dependent antitumor immune responses. See related article by Chen et al., p. 432. This article is highlighted in the In This Issue feature, p. 247.
Identifiants
pubmed: 36302218
pii: 716304
doi: 10.1158/2159-8290.CD-22-0523
pmc: PMC7614152
mid: EMS156558
doi:
Types de publication
Editorial
Research Support, Non-U.S. Gov't
Comment
Langues
eng
Sous-ensembles de citation
IM
Pagination
410-431Subventions
Organisme : European Research Council
ID : 669622
Pays : International
Commentaires et corrections
Type : CommentIn
Type : CommentOn
Type : CommentIn
Informations de copyright
©2022 The Authors; Published by the American Association for Cancer Research.
Références
J Immunother Cancer. 2020 Mar;8(1):
pubmed: 32209603
Mol Syst Biol. 2011 Sep 27;7:533
pubmed: 21952136
Immun Ageing. 2020 Jun 3;17:16
pubmed: 32518575
Nat Rev Cancer. 2021 May;21(5):298-312
pubmed: 33750922
Bioinformatics. 2017 Jan 1;33(1):135-136
pubmed: 27605098
Cell. 2020 Apr 16;181(2):424-441.e21
pubmed: 32234521
Science. 2020 Aug 21;369(6506):
pubmed: 32820093
Semin Immunol. 2018 Dec;40:101275
pubmed: 31088710
Nucleic Acids Res. 2022 Jan 7;50(D1):D543-D552
pubmed: 34723319
Cancer Immunol Res. 2019 Dec;7(12):1984-1997
pubmed: 31540894
Blood. 2021 May 20;137(20):2785-2799
pubmed: 33232972
Bioinformatics. 2010 Sep 1;26(17):2176-82
pubmed: 20610611
Mol Ther. 2012 May;20(5):1046-55
pubmed: 22334019
Cancer Discov. 2023 Feb 6;13(2):432-453
pubmed: 36302222
Annu Rev Pathol. 2010;5:99-118
pubmed: 20078217
Science. 2016 Jan 29;351(6272):aad3867
pubmed: 26823435
Cell. 2019 Oct 31;179(4):813-827
pubmed: 31675495
Science. 2018 Dec 21;362(6421):1416-1422
pubmed: 30573629
Cell. 1997 Mar 7;88(5):593-602
pubmed: 9054499
Med. 2021 Aug 13;2(8):938-950
pubmed: 34617070
BMC Bioinformatics. 2009 Feb 03;10:48
pubmed: 19192299
Nature. 2011 Nov 09;479(7374):547-51
pubmed: 22080947
Science. 2015 Dec 11;350(6266):1387-90
pubmed: 26516200
Ann Appl Stat. 2014 Mar;8(1):309-330
pubmed: 24795787
Cancer Immunol Res. 2020 Oct;8(10):1287-1299
pubmed: 32759362
Cell. 2008 Aug 22;134(4):657-67
pubmed: 18724938
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
PLoS Biol. 2020 Jan 16;18(1):e3000599
pubmed: 31945054
J Immunol. 1998 Nov 15;161(10):5516-24
pubmed: 9820528
Endocrinology. 2017 Jul 1;158(7):2344-2353
pubmed: 28525591
Exp Mol Med. 1998 Mar 31;30(1):1-13
pubmed: 9873816
Oncoimmunology. 2018 Mar 06;7(6):e1438107
pubmed: 29930882
Nature. 2020 Jul;583(7814):127-132
pubmed: 32555459
Sci Rep. 2017 Dec 4;7(1):16878
pubmed: 29203879
Blood. 2000 Nov 1;96(9):3029-39
pubmed: 11049981
Aging (Albany NY). 2016 Feb;8(2):328-44
pubmed: 26878797
Genes Dev. 2020 Dec 1;34(23-24):1565-1576
pubmed: 33262144
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
Mol Cell Proteomics. 2015 Dec;14(12):3105-17
pubmed: 26628741
Nat Rev Immunol. 2012 Dec;12(12):813-20
pubmed: 23175229
J Vis Exp. 2021 Oct 15;(176):
pubmed: 34723952
Sci Data. 2018 Aug 07;5:180157
pubmed: 30084848
Elife. 2017 Dec 11;6:
pubmed: 29227245
Cells. 2020 Mar 10;9(3):
pubmed: 32164335
J Exp Med. 2013 Sep 23;210(10):2057-69
pubmed: 24043758
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Nat Commun. 2019 Jun 3;10(1):2387
pubmed: 31160572
Aging Cell. 2020 Oct;19(10):e13234
pubmed: 32918364
J Invest Dermatol. 2017 Oct;137(10):2197-2207
pubmed: 28647344
Nat Immunol. 2022 Apr;23(4):487-500
pubmed: 35145297
Nat Commun. 2018 Dec 21;9(1):5435
pubmed: 30575733
Nat Rev Clin Oncol. 2021 Sep;18(9):591-602
pubmed: 33976418
Clin Cancer Res. 2017 May 15;23(10):2491-2505
pubmed: 27827318
Cancer Discov. 2022 Jan;12(1):31-46
pubmed: 35022204
Proc Natl Acad Sci U S A. 2017 Feb 28;114(9):E1668-E1677
pubmed: 28193858
Cell. 2001 Aug 10;106(3):255-8
pubmed: 11509172
Exp Mol Med. 2021 Dec;53(12):1834-1841
pubmed: 34916607
Cell. 2013 Nov 21;155(5):1104-18
pubmed: 24238962
Clin Cancer Res. 2015 Feb 15;21(4):687-92
pubmed: 25501578
Nature. 2007 Feb 8;445(7128):656-60
pubmed: 17251933
Nat Commun. 2020 Jun 2;11(1):2760
pubmed: 32488085
Nature. 2013 Feb 21;494(7437):361-5
pubmed: 23376950
Bioinformatics. 2015 Jun 15;31(12):2032-4
pubmed: 25697820
Nucleic Acids Res. 2004 Feb 20;32(3):e34
pubmed: 14978222
Nature. 2022 Nov;611(7935):358-364
pubmed: 36323784
Nat Rev Mol Cell Biol. 2014 Jul;15(7):482-96
pubmed: 24954210
Physiol Rev. 2019 Apr 1;99(2):1047-1078
pubmed: 30648461
J Exp Med. 2006 May 15;203(5):1259-71
pubmed: 16636135
Nat Rev Cancer. 2022 Jun;22(6):340-355
pubmed: 35241831
Cancer Cell. 2010 Nov 16;18(5):485-98
pubmed: 21035406
Cancers (Basel). 2020 Jul 02;12(7):
pubmed: 32630675