Tumor neoantigenicity assessment with CSiN score incorporates clonality and immunogenicity to predict immunotherapy outcomes.
Journal
Science immunology
ISSN: 2470-9468
Titre abrégé: Sci Immunol
Pays: United States
ID NLM: 101688624
Informations de publication
Date de publication:
21 02 2020
21 02 2020
Historique:
received:
29
08
2019
revised:
11
11
2019
accepted:
30
01
2020
entrez:
23
2
2020
pubmed:
23
2
2020
medline:
15
12
2020
Statut:
ppublish
Résumé
Lack of responsiveness to checkpoint inhibitors is a central problem in the modern era of cancer immunotherapy. Tumor neoantigens are critical targets of the host antitumor immune response, and their presence correlates with the efficacy of immunotherapy treatment. Many studies involving assessment of tumor neoantigens principally focus on total neoantigen load, which simplistically treats all neoantigens equally. Neoantigen load has been linked with treatment response and prognosis in some studies but not others. We developed a Cauchy-Schwarz index of Neoantigens (CSiN) score to better account for the degree of concentration of immunogenic neoantigens in truncal mutations. Unlike total neoantigen load determinations, CSiN incorporates the effect of both clonality and MHC binding affinity of neoantigens when characterizing tumor neoantigen profiles. By analyzing the clinical responses in 501 treated patients with cancer (with most receiving checkpoint inhibitors) and the overall survival of 1978 patients with cancer at baseline, we showed that CSiN scores predict treatment response to checkpoint inhibitors and prognosis in patients with melanoma, lung cancer, and kidney cancer. CSiN score substantially outperformed prior genetics-based prediction methods of responsiveness and fills an important gap in research involving assessment of tumor neoantigen burden.
Identifiants
pubmed: 32086382
pii: 5/44/eaaz3199
doi: 10.1126/sciimmunol.aaz3199
pmc: PMC7239327
mid: NIHMS1581910
pii:
doi:
Substances chimiques
Antigens, Neoplasm
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : P30 CA142543
Pays : United States
Organisme : NIEHS NIH HHS
ID : R03 ES026397
Pays : United States
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Références
Nucleic Acids Res. 2013 Aug;41(14):e142
pubmed: 23748956
Nat Genet. 2017 Aug;49(8):1211-1218
pubmed: 28671688
Nat Med. 2003 May;9(5):562-7
pubmed: 12704383
Cell Res. 2017 Jan;27(1):11-37
pubmed: 28025978
Front Immunol. 2017 Dec 19;8:1848
pubmed: 29312332
Nature. 2015 Apr 30;520(7549):692-6
pubmed: 25901682
Nat Commun. 2016 Nov 21;7:13404
pubmed: 27869121
N Engl J Med. 2015 Jan 22;372(4):311-9
pubmed: 25482239
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
EBioMedicine. 2015 Jan 19;2(2):92-3
pubmed: 26137543
N Engl J Med. 2014 Dec 4;371(23):2189-2199
pubmed: 25409260
Oncoimmunology. 2017 Jun 16;6(8):e1338996
pubmed: 28920005
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Front Immunol. 2017 Dec 13;8:1815
pubmed: 29326702
J Clin Invest. 2017 Aug 1;127(8):2930-2940
pubmed: 28650338
Nat Rev Cancer. 2017 Apr;17(4):209-222
pubmed: 28233802
Cancer Discov. 2017 Dec;7(12):1420-1435
pubmed: 29025772
Science. 2018 Feb 16;359(6377):801-806
pubmed: 29301960
Cell. 2017 Nov 2;171(4):934-949.e16
pubmed: 29033130
Science. 2015 Apr 3;348(6230):124-8
pubmed: 25765070
Science. 2015 Oct 9;350(6257):207-211
pubmed: 26359337
N Engl J Med. 2003 Jan 16;348(3):203-13
pubmed: 12529460
Nat Biotechnol. 2006 Jul;24(7):817-9
pubmed: 16767078
Science. 2016 Jun 10;352(6291):1337-41
pubmed: 27198675
Nat Biotechnol. 2013 Mar;31(3):213-9
pubmed: 23396013
Nat Genet. 2018 Sep;50(9):1271-1281
pubmed: 30150660
Sci Transl Med. 2015 Apr 15;7(283):283ra54
pubmed: 25877892
Nature. 2017 Jul 13;547(7662):217-221
pubmed: 28678778
Cancer Discov. 2018 Sep;8(9):1142-1155
pubmed: 29884728
J Clin Invest. 2018 Feb 1;128(2):805-815
pubmed: 29337305
Oncologist. 2017 May;22(5):585-591
pubmed: 28438889
Genome Res. 2010 Sep;20(9):1297-303
pubmed: 20644199
Nature. 2014 Jul 31;511(7511):543-50
pubmed: 25079552
Cancer Immunol Res. 2016 May;4(5):463-71
pubmed: 26980598
Blood Cancer J. 2017 Sep 22;7(9):e612
pubmed: 28937974
Cell. 2017 Jun 15;169(7):1327-1341.e23
pubmed: 28622513
Nature. 2017 Nov 23;551(7681):512-516
pubmed: 29132146
Nat Med. 2017 Jun;23(6):703-713
pubmed: 28481359
Cell. 2016 Mar 24;165(1):35-44
pubmed: 26997480
Clin Dev Immunol. 2011;2011:439752
pubmed: 22162711
Mol Ther. 2014 Jul;22(7):1388-1395
pubmed: 24686272
Oncoimmunology. 2012 Jan 1;1(1):48-55
pubmed: 22720211
N Engl J Med. 2016 Nov 10;375(19):1823-1833
pubmed: 27718847
Cancer. 2018 Jan 15;124(2):248-261
pubmed: 29211297
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
Nature. 2014 Aug 21;512(7514):324-7
pubmed: 25043048
Cell. 2017 Jan 26;168(3):542
pubmed: 28129544
Nat Genet. 2011 May;43(5):491-8
pubmed: 21478889
Science. 2014 May 9;344(6184):641-5
pubmed: 24812403
Cell. 2015 Jun 18;161(7):1681-96
pubmed: 26091043
Nat Commun. 2016 Aug 23;7:12460
pubmed: 27549343
Cancer Discov. 2017 Mar;7(3):264-276
pubmed: 28031159
Nat Genet. 2013 Aug;45(8):860-7
pubmed: 23797736
Science. 2016 Mar 25;351(6280):1463-9
pubmed: 26940869
Nature. 2017 Nov 23;551(7681):517-520
pubmed: 29132144
Cell. 2018 Apr 19;173(3):581-594.e12
pubmed: 29656895
Nat Biotechnol. 2017 Feb 8;35(2):97
pubmed: 28178261
Nature. 2009 Nov 5;462(7269):108-12
pubmed: 19847166
Lancet Oncol. 2017 Aug;18(8):1009-1021
pubmed: 28694034
Nature. 2015 Nov 12;527(7577):249-53
pubmed: 26503055
Nature. 2013 Jul 4;499(7456):43-9
pubmed: 23792563
Cancer Cell. 2018 May 14;33(5):843-852.e4
pubmed: 29657128
Immunogenetics. 2015 Nov;67(11-12):641-50
pubmed: 26416257
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Cancer. 2016 Feb 1;122(3):367-77
pubmed: 26540029
Nat Med. 2018 Dec;24(12):1941
pubmed: 30291359
BMC Bioinformatics. 2013 Jan 16;14:7
pubmed: 23323831
Nature. 2016 Aug 4;536(7614):91-5
pubmed: 27350335
Curr Protoc Bioinformatics. 2013;43:11.10.1-11.10.33
pubmed: 25431634
Nature. 2012 Sep 27;489(7417):519-25
pubmed: 22960745
Front Oncol. 2018 Mar 28;8:86
pubmed: 29644214
Nat Methods. 2015 Oct;12(10):966-8
pubmed: 26258291
Genome Res. 2012 Mar;22(3):568-76
pubmed: 22300766
Nat Med. 2018 Jun;24(6):749-757
pubmed: 29867230
Genome Biol. 2016 Nov 17;17(1):231
pubmed: 27855702
Bioinformatics. 2012 Jul 15;28(14):1811-7
pubmed: 22581179
J Immunol. 1994 Dec 15;153(12):5586-92
pubmed: 7527444
Nat Biotechnol. 2014 Dec;32(12):1202-12
pubmed: 24880487
Cancer Res. 2016 Apr 15;76(8):2177-85
pubmed: 26862115
Nat Genet. 2019 Feb;51(2):202-206
pubmed: 30643254
Clin Cancer Res. 2013 Oct 1;19(19):5300-9
pubmed: 24089443