Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy.
Immune checkpoint inhibition
NECTIN2
Neuroblastoma
PD-1
PD-L1
Pediatric oncology
TIGIT
immune evasion
immunotherapy
tumor microenvironment
Journal
Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617
Informations de publication
Date de publication:
12 02 2024
12 02 2024
Historique:
received:
15
02
2023
revised:
10
11
2023
accepted:
11
12
2023
medline:
15
2
2024
pubmed:
6
1
2024
entrez:
5
1
2024
Statut:
ppublish
Résumé
Pediatric patients with high-risk neuroblastoma have poor survival rates and urgently need more effective treatment options with less side effects. Since novel and improved immunotherapies may fill this need, we dissect the immunoregulatory interactions in neuroblastoma by single-cell RNA-sequencing of 24 tumors (10 pre- and 14 post-chemotherapy, including 5 pairs) to identify strategies for optimizing immunotherapy efficacy. Neuroblastomas are infiltrated by natural killer (NK), T and B cells, and immunosuppressive myeloid populations. NK cells show reduced cytotoxicity and T cells have a dysfunctional profile. Interaction analysis reveals a vast immunoregulatory network and identifies NECTIN2-TIGIT as a crucial immune checkpoint. Combined blockade of TIGIT and PD-L1 significantly reduces neuroblastoma growth, with complete responses (CR) in vivo. Moreover, addition of TIGIT+PD-L1 blockade to standard relapse treatment in a chemotherapy-resistant Th-ALK
Identifiants
pubmed: 38181797
pii: S1535-6108(23)00436-1
doi: 10.1016/j.ccell.2023.12.008
pmc: PMC10864003
pii:
doi:
Substances chimiques
B7-H1 Antigen
0
Receptors, Immunologic
0
TIGIT protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
283-300.e8Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 28278
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests H.C., A.R., and R.B. are employed at Hoffman-La Roche. R.B. also is an employee of Genentech, a member of the Roche Group. J.A. has founder shares in Autolus Ltd. J.A. and L.C. have received research funding from Roche for in vivo work. J.M. has received research funding from Roche for in vitro work. J.C.G is a member of a DMC for trials sponsored by YmAbs Therapeutics and University of Birmingham, and has had consulting roles for EUSA Pharma, YmAbs Therapeutics, Celgene, Servier and Norgine.
Références
Cell. 2019 Feb 7;176(4):775-789.e18
pubmed: 30595452
Clin Cancer Res. 2022 Mar 01;28(5):882-892
pubmed: 34844977
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Cell Mol Immunol. 2020 Jan;17(1):27-35
pubmed: 31853000
Nat Immunol. 2019 Feb;20(2):163-172
pubmed: 30643263
J Clin Invest. 2012 Sep;122(9):3260-70
pubmed: 22863621
Immunity. 2022 Mar 8;55(3):512-526.e9
pubmed: 35263569
Nature. 2018 Jun;558(7710):454-459
pubmed: 29899446
J Exp Med. 2017 Feb;214(2):381-400
pubmed: 28115575
Ann Oncol. 2022 Feb;33(2):169-180
pubmed: 34800678
Proc Natl Acad Sci U S A. 2019 Jun 18;116(25):12410-12415
pubmed: 31152140
Science. 2015 Jan 23;347(6220):1260419
pubmed: 25613900
Nat Cancer. 2020 May;1(5):493-506
pubmed: 33409501
J Immunother Cancer. 2022 Aug;10(8):
pubmed: 36054452
Nat Commun. 2021 May 13;12(1):2782
pubmed: 33986293
Nat Med. 2008 Nov;14(11):1264-70
pubmed: 18978797
Nucleic Acids Res. 2002 Jan 1;30(1):207-10
pubmed: 11752295
Nat Commun. 2020 Mar 11;11(1):1310
pubmed: 32161258
Nat Immunol. 2019 Mar;20(3):326-336
pubmed: 30778252
Cell. 2021 Feb 4;184(3):792-809.e23
pubmed: 33545035
N Engl J Med. 2023 Apr 6;388(14):1284-1295
pubmed: 37018492
J Immunol. 2016 Nov 15;197(10):3806-3819
pubmed: 27815440
Cancer Cell. 2012 Jul 10;22(1):117-30
pubmed: 22789543
J Clin Oncol. 2010 May 20;28(15):2625-34
pubmed: 20404250
Cell. 2018 Nov 1;175(4):984-997.e24
pubmed: 30388455
Cancers (Basel). 2023 Jun 23;15(13):
pubmed: 37444427
Cytokine. 2018 Jun;106:114-124
pubmed: 29089178
Eur J Cancer. 2014 Feb;50(3):628-37
pubmed: 24321263
Lancet Oncol. 2020 Apr;21(4):541-550
pubmed: 32192573
Clin Cancer Res. 2021 Nov 1;27(21):5742-5752
pubmed: 34127507
Cell. 2019 Oct 31;179(4):829-845.e20
pubmed: 31675496
Eur J Cancer. 2021 Jun;150:53-62
pubmed: 33892407
Nat Commun. 2019 Oct 17;10(1):4706
pubmed: 31624246
Nat Biotechnol. 2014 Sep;32(9):903-14
pubmed: 25150838
Lancet Oncol. 2017 Jul;18(7):946-957
pubmed: 28549783
Front Oncol. 2021 Jul 21;11:709210
pubmed: 34367994
Front Immunol. 2019 Aug 07;10:1823
pubmed: 31440237
Lancet Oncol. 2022 Jun;23(6):781-792
pubmed: 35576957
Nat Commun. 2021 Feb 17;12(1):1088
pubmed: 33597522
Cell. 2011 Jan 21;144(2):296-309
pubmed: 21241896
Immunity. 2017 Dec 19;47(6):1129-1141.e5
pubmed: 29246443
Nat Med. 2022 Feb;28(2):333-344
pubmed: 35027753
J Clin Oncol. 2022 Feb 1;40(4):335-344
pubmed: 34871104
Nat Rev Cancer. 2013 Jun;13(6):397-411
pubmed: 23702928
Immunity. 2007 Oct;27(4):670-84
pubmed: 17950003
Nat Commun. 2020 Feb 18;11(1):931
pubmed: 32071302
Cancers (Basel). 2020 Jan 28;12(2):
pubmed: 32013055
Nat Med. 2023 Jun;29(6):1379-1388
pubmed: 37188782
Immunity. 2016 Nov 15;45(5):1135-1147
pubmed: 27851914
Nat Commun. 2022 Apr 27;13(1):2274
pubmed: 35477960
Science. 2021 Dec 17;374(6574):abe6474
pubmed: 34914499
J Immunother Cancer. 2020 May;8(1):
pubmed: 32414861
Cancer Res. 2017 Dec 1;77(23):6667-6678
pubmed: 28993412
Nat Immunol. 2014 Nov;15(11):1070-8
pubmed: 25263123
Blood. 2015 Apr 16;125(16):2507-18
pubmed: 25733583
Cancer Discov. 2021 Jan;11(1):34-44
pubmed: 33277307
J Natl Cancer Inst. 2009 Aug 19;101(16):1131-40
pubmed: 19648511
Nat Immunol. 2018 Jul;19(7):723-732
pubmed: 29915296
Blood. 2011 Dec 1;118(23):6050-6
pubmed: 21984804
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Immunity. 2017 Jan 17;46(1):78-91
pubmed: 28099866
Br J Cancer. 2010 May 25;102(11):1555-77
pubmed: 20502460
PLoS One. 2018 Nov 30;13(11):e0207255
pubmed: 30500835
Prog Lipid Res. 2019 Oct;76:101010
pubmed: 31682868
J Clin Invest. 2015 Nov 2;125(11):4053-62
pubmed: 26413872
J Immunother Cancer. 2022 Dec;10(12):
pubmed: 36521927
Ugeskr Laeger. 2008 Jan 28;170(5):328-30
pubmed: 18252159
Genome Res. 2012 Sep;22(9):1760-74
pubmed: 22955987
Nat Immunol. 2022 May;23(5):660-670
pubmed: 35241833
Nat Commun. 2018 Jul 2;9(1):2570
pubmed: 29967419
Haematologica. 2014 May;99(5):67-9
pubmed: 24561794
Cell Syst. 2016 Oct 26;3(4):385-394.e3
pubmed: 27693023
Methods Mol Biol. 2011;694:49-61
pubmed: 21082427
Mol Ther. 2007 Apr;15(4):825-33
pubmed: 17299405
Lancet Oncol. 2020 Jan;21(1):121-133
pubmed: 31812554
N Engl J Med. 2010 Sep 30;363(14):1324-34
pubmed: 20879881
J Clin Oncol. 2021 Oct 10;39(29):3229-3241
pubmed: 34319759
Cell Rep. 2019 Feb 5;26(6):1627-1640.e7
pubmed: 30726743
Genome Biol. 2020 Mar 5;21(1):57
pubmed: 32138770
Science. 2016 Apr 8;352(6282):189-96
pubmed: 27124452
Mol Ther. 2017 Sep 6;25(9):2214-2224
pubmed: 28602436
Clin Cancer Res. 2014 Jan 1;20(1):44-55
pubmed: 24045181
Clin Transl Immunology. 2021 Jan 10;10(1):e1238
pubmed: 33456775
Cancer Lett. 2018 Apr 10;419:210-221
pubmed: 29414305
Nat Rev Drug Discov. 2021 Jul;20(7):531-550
pubmed: 33972771
Cancers (Basel). 2021 Apr 26;13(9):
pubmed: 33926057
Cancer Cell. 2014 Dec 8;26(6):923-937
pubmed: 25465800
PLoS Biol. 2020 Jul 14;18(7):e3000410
pubmed: 32663219
Nat Immunol. 2010 Oct;11(10):889-96
pubmed: 20856220
Sci Transl Med. 2020 Nov 25;12(571):
pubmed: 33239386
Nat Rev Immunol. 2022 Apr;22(4):209-223
pubmed: 34253904
Cancer Immunol Immunother. 2005 Apr;54(4):400-6
pubmed: 15449039
Cell Rep Med. 2022 Jun 21;3(6):100657
pubmed: 35688160
Nat Rev Drug Discov. 2022 Jul;21(7):509-528
pubmed: 34937915
Nat Protoc. 2020 Apr;15(4):1484-1506
pubmed: 32103204
J Pers Med. 2021 Aug 30;11(9):
pubmed: 34575646
Cancer Lett. 2020 May 1;477:131-143
pubmed: 32061950
Cancer Cell. 2021 Dec 13;39(12):1623-1642.e20
pubmed: 34739845
Physiol Genomics. 2005 May 11;21(3):396-403
pubmed: 15769904
Mol Ther Nucleic Acids. 2021 Oct 19;26:1115-1129
pubmed: 34786214
Nat Immunol. 2011 Apr;12(4):304-11
pubmed: 21378976
Eur J Cancer. 2021 Feb;144:123-150
pubmed: 33341446