Spatially resolved analyses link genomic and immune diversity and reveal unfavorable neutrophil activation in melanoma.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
15 04 2020
15 04 2020
Historique:
received:
17
06
2019
accepted:
11
03
2020
entrez:
17
4
2020
pubmed:
17
4
2020
medline:
25
7
2020
Statut:
epublish
Résumé
Complex tumor microenvironmental (TME) features influence the outcome of cancer immunotherapy (IO). Here we perform immunogenomic analyses on 67 intratumor sub-regions of a PD-1 inhibitor-resistant melanoma tumor and 2 additional metastases arising over 8 years, to characterize TME interactions. We identify spatially distinct evolution of copy number alterations influencing local immune composition. Sub-regions with chromosome 7 gain display a relative lack of leukocyte infiltrate but evidence of neutrophil activation, recapitulated in The Cancer Genome Atlas (TCGA) samples, and associated with lack of response to IO across three clinical cohorts. Whether neutrophil activation represents cause or consequence of local tumor necrosis requires further study. Analyses of T-cell clonotypes reveal the presence of recurrent priming events manifesting in a dominant T-cell clonotype over many years. Our findings highlight the links between marked levels of genomic and immune heterogeneity within the physical space of a tumor, with implications for biomarker evaluation and immunotherapy response.
Identifiants
pubmed: 32296058
doi: 10.1038/s41467-020-15538-9
pii: 10.1038/s41467-020-15538-9
pmc: PMC7160105
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1839Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NIAMS NIH HHS
ID : T32 AR065971
Pays : United States
Références
Cell. 2017 Nov 2;171(4):934-949.e16
pubmed: 29033130
OMICS. 2012 May;16(5):284-7
pubmed: 22455463
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
Nat Rev Cancer. 2009 Apr;9(4):239-52
pubmed: 19279573
Nature. 2009 Nov 5;462(7269):108-12
pubmed: 19847166
Genome Biol. 2016 Dec 1;17(1):249
pubmed: 27908289
Bioinformatics. 2015 Jan 15;31(2):166-9
pubmed: 25260700
Bioinformatics. 2013 Jan 15;29(2):189-96
pubmed: 23175756
Ann Oncol. 2015 Jan;26(1):64-70
pubmed: 25319062
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
N Engl J Med. 2014 Dec 4;371(23):2189-2199
pubmed: 25409260
BMC Bioinformatics. 2015 May 28;16:175
pubmed: 26017500
PLoS One. 2010 May 24;5(5):e10770
pubmed: 20520718
Science. 2015 Oct 9;350(6257):207-211
pubmed: 26359337
J Mol Diagn. 2004 Nov;6(4):343-7
pubmed: 15507673
Biostatistics. 2007 Jan;8(1):118-27
pubmed: 16632515
Cell. 2010 Apr 2;141(1):39-51
pubmed: 20371344
Oncotarget. 2016 Mar 1;7(9):10051-63
pubmed: 26840267
N Engl J Med. 2017 Jun 1;376(22):2109-2121
pubmed: 28445112
Front Oncol. 2018 Nov 26;8:549
pubmed: 30534534
Blood. 2009 Nov 5;114(19):4099-107
pubmed: 19706884
Ann Oncol. 2017 Oct 01;28(10):2472-2480
pubmed: 28961847
Nat Biotechnol. 2013 Mar;31(3):213-9
pubmed: 23396013
Bioinformatics. 2010 Jun 15;26(12):1572-3
pubmed: 20427518
Nucleic Acids Res. 2013 Aug;41(14):e142
pubmed: 23748956
Genome Biol. 2014;15(12):550
pubmed: 25516281
Cell. 2015 Jan 15;160(1-2):48-61
pubmed: 25594174
J Immunol. 2005 Aug 15;175(4):2261-9
pubmed: 16081794
Nat Commun. 2013;4:2680
pubmed: 24157944
Nat Methods. 2015 May;12(5):453-7
pubmed: 25822800
N Engl J Med. 2012 Mar 8;366(10):883-892
pubmed: 22397650
Cancer Discov. 2014 Jul;4(7):816-27
pubmed: 24771846
Cell. 2016 Mar 24;165(1):35-44
pubmed: 26997480
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Nat Biotechnol. 2015 Nov;33(11):1152-8
pubmed: 26372948
Nat Commun. 2016 Jan 25;7:10500
pubmed: 26806015
Nat Methods. 2014 Apr;11(4):396-8
pubmed: 24633410
Clin Cancer Res. 2012 Oct 1;18(19):5329-40
pubmed: 22850568
Cancer Discov. 2016 Aug;6(8):827-37
pubmed: 27301722
Nature. 2014 Nov 27;515(7528):568-71
pubmed: 25428505
Bioinformatics. 2014 Oct;30(19):2811-2
pubmed: 24930139
Cancer Res. 2018 Oct 15;78(20):5970-5979
pubmed: 30154148
Bioinformatics. 2016 Sep 15;32(18):2847-9
pubmed: 27207943
Crit Rev Immunol. 2004;24(4):267-96
pubmed: 15588226
Cancer Cell. 2018 Mar 12;33(3):450-462.e10
pubmed: 29533785
Cell. 2015 Jun 18;161(7):1681-96
pubmed: 26091043
Cancer Res. 2010 Jul 1;70(13):5213-9
pubmed: 20551059
Cell Immunol. 2018 Sep;331:30-37
pubmed: 29773224
Bioinformatics. 2011 Oct 1;27(19):2648-54
pubmed: 21828086
Cancer Res. 2008 Jan 15;68(2):450-6
pubmed: 18199539
J Immunother Cancer. 2014 Oct 14;2(1):36
pubmed: 25317334
Bioinformatics. 2014 Feb 01;30(3):428-30
pubmed: 24336642
Nature. 2019 May;569(7755):270-274
pubmed: 31043744
J Pathol. 2013 Dec;231(4):424-32
pubmed: 24122851
Bioinformatics. 2015 Nov 15;31(22):3718-20
pubmed: 26209431
BMC Bioinformatics. 2013 Jan 16;14:7
pubmed: 23323831
Bioinformatics. 2009 Nov 1;25(21):2865-71
pubmed: 19561018
Neoplasia. 2013 Dec;15(12):1371-8
pubmed: 24403859
NPJ Genom Med. 2017;2:
pubmed: 28819565
Sci Transl Med. 2017 Mar 1;9(379):
pubmed: 28251903
Genome Biol. 2013 Apr 25;14(4):R36
pubmed: 23618408
Cell Rep. 2019 Mar 5;26(10):2651-2666.e6
pubmed: 30840888
Genome Biol. 2016 Aug 22;17(1):174
pubmed: 27549193
Cancer Discov. 2016 Feb;6(2):202-16
pubmed: 26645196
Nature. 2005 Jul 7;436(7047):117-22
pubmed: 16001072
Science. 2016 Apr 8;352(6282):189-96
pubmed: 27124452
Bioinformatics. 2011 Feb 15;27(4):592-3
pubmed: 21169378
Blood. 2012 Aug 23;120(8):1633-46
pubmed: 22623625
Genome Biol. 2007;8(9):R183
pubmed: 17784955
Bioinformatics. 2015 Feb 15;31(4):608-9
pubmed: 25677125
Stat Appl Genet Mol Biol. 2004;3:Article3
pubmed: 16646809
Nat Commun. 2013;4:2612
pubmed: 24113773
Nat Commun. 2017 Jan 16;8:14049
pubmed: 28091601
Immunogenetics. 2013 Oct;65(10):711-24
pubmed: 23900783
Nature. 2015 Jul 9;523(7559):231-5
pubmed: 25970248
Int J Epidemiol. 2012 Feb;41(1):200-9
pubmed: 22422453
N Engl J Med. 2016 Sep 1;375(9):819-29
pubmed: 27433843
Nat Genet. 2014 Mar;46(3):225-233
pubmed: 24487277
Ann Oncol. 2017 Dec 01;28(12):3076-3082
pubmed: 28950321
Nucleic Acids Res. 2008 Feb;36(2):e11
pubmed: 18178591
Clin Cancer Res. 2013 Mar 1;19(5):1225-31
pubmed: 23307859
Nat Biotechnol. 2015 May;33(5):495-502
pubmed: 25867923