Immunosuppressive niche engineering at the onset of human colorectal cancer.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
04 04 2022
04 04 2022
Historique:
received:
10
08
2021
accepted:
24
02
2022
entrez:
5
4
2022
pubmed:
6
4
2022
medline:
7
4
2022
Statut:
epublish
Résumé
The evolutionary dynamics of tumor initiation remain undetermined, and the interplay between neoplastic cells and the immune system is hypothesized to be critical in transformation. Colorectal cancer (CRC) presents a unique opportunity to study the transition to malignancy as pre-cancers (adenomas) and early-stage cancers are frequently resected. Here, we examine tumor-immune eco-evolutionary dynamics from pre-cancer to carcinoma using a computational model, ecological analysis of digital pathology data, and neoantigen prediction in 62 patient samples. Modeling predicted recruitment of immunosuppressive cells would be the most common driver of transformation. As predicted, ecological analysis reveals that progressed adenomas co-localized with immunosuppressive cells and cytokines, while benign adenomas co-localized with a mixed immune response. Carcinomas converge to a common immune "cold" ecology, relaxing selection against immunogenicity and high neoantigen burdens, with little evidence for PD-L1 overexpression driving tumor initiation. These findings suggest re-engineering the immunosuppressive niche may prove an effective immunotherapy in CRC.
Identifiants
pubmed: 35379804
doi: 10.1038/s41467-022-29027-8
pii: 10.1038/s41467-022-29027-8
pmc: PMC8979971
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1798Subventions
Organisme : NCI NIH HHS
ID : U54 CA217376
Pays : United States
Organisme : Wellcome Trust
ID : 105104/Z/14/Z
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : U54 CA193489
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA232382
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206314/Z/17/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202778/Z/16/Z
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A19771
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202778/B/16/Z
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A22909
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
Références
Front Immunol. 2017 Jul 14;8:828
pubmed: 28769933
Bioinformatics. 2010 Mar 1;26(5):589-95
pubmed: 20080505
Cancer Discov. 2018 Jun;8(6):730-749
pubmed: 29510987
Cancer Cell. 2010 Feb 17;17(2):121-34
pubmed: 20138013
Int J Mol Sci. 2017 Jun 21;18(6):
pubmed: 28635639
Front Immunol. 2019 Aug 20;10:1875
pubmed: 31481956
N Engl J Med. 2012 Feb 23;366(8):687-96
pubmed: 22356322
Nat Biomed Eng. 2018 Aug;2(8):589-599
pubmed: 30956894
Cell. 1996 Oct 18;87(2):159-70
pubmed: 8861899
Cancer Res. 2011 May 15;71(10):3540-51
pubmed: 21430066
Science. 2011 Mar 25;331(6024):1565-70
pubmed: 21436444
Front Biosci. 2008 May 01;13:5094-107
pubmed: 18508572
Cancer Cell. 2015 Apr 13;27(4):450-61
pubmed: 25858804
Nat Genet. 2015 Mar;47(3):209-16
pubmed: 25665006
Nat Immunol. 2002 Nov;3(11):999-1005
pubmed: 12407407
Cell. 2017 Nov 30;171(6):1259-1271.e11
pubmed: 29107330
Nature. 2019 Jul;571(7766):570-575
pubmed: 31243362
Clin Cancer Res. 2010 Dec 15;16(24):6019-28
pubmed: 20924130
Semin Cancer Biol. 2015 Dec;35 Suppl:S185-S198
pubmed: 25818339
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Nat Genet. 2020 Oct;52(10):1057-1066
pubmed: 32929288
J Pathol. 2013 Jan;229(2):176-85
pubmed: 23096265
Nat Immunol. 2002 Nov;3(11):991-8
pubmed: 12407406
Science. 2006 Sep 29;313(5795):1960-4
pubmed: 17008531
Br J Cancer. 2006 Jan 30;94(2):333-7
pubmed: 16333309
Nat Genet. 2018 Jun;50(6):895-903
pubmed: 29808029
Nat Biotechnol. 2015 Nov;33(11):1152-8
pubmed: 26372948
Cancer Control. 2020 Jan-Dec;27(1):1073274820911058
pubmed: 32129079
Nat Commun. 2020 Feb 25;11(1):1035
pubmed: 32098957
Mol Cancer Ther. 2003 Sep;2(9):919-27
pubmed: 14555711
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
Cell. 1990 Jun 1;61(5):759-67
pubmed: 2188735
Clin Cancer Res. 2017 Jul 1;23(13):3241-3250
pubmed: 28341752
Cancer Res. 2021 Feb 15;81(4):1135-1147
pubmed: 33172930
Genome Biol. 2015 Mar 31;16:64
pubmed: 25853550
Nature. 2017 Nov 23;551(7681):517-520
pubmed: 29132144
Am J Cancer Res. 2012;2(2):204-13
pubmed: 22432059
Nat Rev Gastroenterol Hepatol. 2019 Jun;16(6):361-375
pubmed: 30886395
Nucleic Acids Res. 2015 May 19;43(9):e61
pubmed: 25722372
Cancer Cell. 2014 Jun 16;25(6):809-821
pubmed: 24909985
N Engl J Med. 2005 Dec 22;353(25):2654-66
pubmed: 16371631
Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11515-20
pubmed: 11562487
Cancer. 1975 Dec;36(6):2251-70
pubmed: 1203876
Eur J Immunol. 2010 Aug;40(8):2296-307
pubmed: 20468007
Immunity. 2014 Jul 17;41(1):14-20
pubmed: 25035950
Biometrics. 2006 Mar;62(1):245-53
pubmed: 16542252
J Immunol. 2017 Nov 1;199(9):3360-3368
pubmed: 28978689
Sci Rep. 2019 Mar 26;9(1):5233
pubmed: 30914743
Nat Rev Cancer. 2014 Feb;14(2):135-46
pubmed: 24457417
J Clin Oncol. 2009 Dec 10;27(35):5944-51
pubmed: 19858404
Curr Protoc Bioinformatics. 2013;43:11.10.1-11.10.33
pubmed: 25431634
Cell Rep. 2016 Apr 26;15(4):857-865
pubmed: 27149842
Science. 2010 May 14;328(5980):876-8
pubmed: 20466926
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Nature. 2006 Jun 22;441(7096):1015-9
pubmed: 16791201
Nature. 2013 Apr 25;496(7446):445-55
pubmed: 23619691
Nat Ecol Evol. 2018 Oct;2(10):1661-1672
pubmed: 30177804
J Gastrointest Oncol. 2018 Feb;9(1):160-169
pubmed: 29564182
Gut. 1996 Sep;39(3):449-56
pubmed: 8949653
Cell. 2010 Mar 19;140(6):883-99
pubmed: 20303878
N Engl J Med. 2010 Mar 11;362(10):875-85
pubmed: 20220182
Nature. 2019 Mar;567(7749):479-485
pubmed: 30894752
Nat Rev Cancer. 2016 Jul;16(7):431-46
pubmed: 27282249
Gastroenterology. 2013 Jan;144(1):53-5
pubmed: 22999960
Gut. 2012 Oct;61(10):1439-46
pubmed: 22156981