Cancer immunotherapies transition endothelial cells into HEVs that generate TCF1
-tT(EX)
antiangiogenic immunotherapy
endothelial fate mapping
high-endothelial venule
immune checkpoint blockade
lymphotoxin beta receptor
multiplex immunohistochemistry
pT(EX)
single-cell RNA sequencing
t
tertiary lymphoid structure
Journal
Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617
Informations de publication
Date de publication:
12 12 2022
12 12 2022
Historique:
received:
23
12
2021
revised:
20
07
2022
accepted:
04
11
2022
pubmed:
25
11
2022
medline:
16
12
2022
entrez:
24
11
2022
Statut:
ppublish
Résumé
The lack of T cell infiltrates is a major obstacle to effective immunotherapy in cancer. Conversely, the formation of tumor-associated tertiary-lymphoid-like structures (TA-TLLSs), which are the local site of humoral and cellular immune responses against cancers, is associated with good prognosis, and they have recently been detected in immune checkpoint blockade (ICB)-responding patients. However, how these lymphoid aggregates develop remains poorly understood. By employing single-cell transcriptomics, endothelial fate mapping, and functional multiplex immune profiling, we demonstrate that antiangiogenic immune-modulating therapies evoke transdifferentiation of postcapillary venules into inflamed high-endothelial venules (HEVs) via lymphotoxin/lymphotoxin beta receptor (LT/LTβR) signaling. In turn, tumor HEVs boost intratumoral lymphocyte influx and foster permissive lymphocyte niches for PD1
Identifiants
pubmed: 36423635
pii: S1535-6108(22)00549-9
doi: 10.1016/j.ccell.2022.11.002
pmc: PMC9899876
mid: NIHMS1850840
pii:
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
1600-1618.e10Subventions
Organisme : NCI NIH HHS
ID : R01 CA201537
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests G.B. has received research funding from Oncurious NV and is listed as an inventor on patent applications filed by Oncurious NV related to the subject matter of this work. The other authors declare no competing interests.
Références
Cancer Cell. 2022 Mar 14;40(3):318-334.e9
pubmed: 35120598
Nature. 2011 Nov 13;479(7374):542-6
pubmed: 22080953
Nat Rev Cancer. 2019 Jun;19(6):307-325
pubmed: 31092904
Nat Biotechnol. 2020 Dec;38(12):1408-1414
pubmed: 32747759
Science. 2020 Jan 24;367(6476):405-411
pubmed: 31974247
Immunity. 2001 Jul;15(1):115-26
pubmed: 11485743
Nature. 2019 Dec;576(7787):465-470
pubmed: 31827286
Science. 2015 Apr 3;348(6230):69-74
pubmed: 25838375
Trends Immunol. 2012 Jun;33(6):297-305
pubmed: 22622061
Nat Protoc. 2014 Jan;9(1):171-81
pubmed: 24385147
J Immunol. 2021 Jan 15;206(2):273-281
pubmed: 33397741
Cell. 2017 Nov 2;171(4):934-949.e16
pubmed: 29033130
Nature. 2018 Aug;560(7719):494-498
pubmed: 30089906
J Clin Invest. 2017 Aug 1;127(8):2930-2940
pubmed: 28650338
N Engl J Med. 2010 Aug 19;363(8):711-23
pubmed: 20525992
Nat Immunol. 2019 Mar;20(3):326-336
pubmed: 30778252
Sci Transl Med. 2017 Apr 12;9(385):
pubmed: 28404866
Elife. 2020 Feb 14;9:
pubmed: 32057296
Cell Rep. 2019 Mar 12;26(11):3116-3131.e5
pubmed: 30865898
Immunity. 2016 Oct 18;45(4):877-888
pubmed: 27760341
Nat Biotechnol. 2019 Apr;37(4):451-460
pubmed: 30899105
Nat Methods. 2020 Feb;17(2):159-162
pubmed: 31819264
Nat Commun. 2021 Jun 25;12(1):3969
pubmed: 34172722
IEEE Trans Image Process. 2009 Oct;18(10):2340-54
pubmed: 19520638
Nat Commun. 2015 May 13;6:7114
pubmed: 25968334
Cancer Discov. 2020 Feb;10(2):185-197
pubmed: 31974169
Cancer Cell. 2020 Mar 16;37(3):421
pubmed: 32183954
N Engl J Med. 2012 Jun 28;366(26):2443-54
pubmed: 22658127
Cell Rep. 2021 Jul 20;36(3):109422
pubmed: 34289373
Nat Med. 2014 Jun;20(6):607-15
pubmed: 24793239
Nat Med. 2001 Sep;7(9):987-9
pubmed: 11533692
J Pathol. 2018 Jun;245(2):209-221
pubmed: 29603739
Annu Rev Immunol. 2004;22:129-56
pubmed: 15032576
Immunity. 2019 Jan 15;50(1):195-211.e10
pubmed: 30635237
Immunity. 2019 Jan 15;50(1):181-194.e6
pubmed: 30635236
Nat Immunol. 2012 Nov;13(11):1118-28
pubmed: 23023392
Nat Methods. 2017 Nov;14(11):1083-1086
pubmed: 28991892
Nature. 2014 Nov 27;515(7528):568-71
pubmed: 25428505
Sci Rep. 2017 Dec 4;7(1):16878
pubmed: 29203879
Nature. 2014 Nov 27;515(7528):563-7
pubmed: 25428504
Nat Med. 2021 May;27(5):820-832
pubmed: 33958794
Hypertension. 2016 Apr;67(4):674-80
pubmed: 26902490
Bioinformatics. 2021 Mar 28;:
pubmed: 33774659
Genome Res. 2003 Nov;13(11):2498-504
pubmed: 14597658
Front Immunol. 2017 Feb 03;8:45
pubmed: 28217126
Oncoimmunology. 2022 Jul 1;11(1):2093054
pubmed: 35800155
J Immunother Cancer. 2020 Oct;8(2):
pubmed: 33093155
Front Immunol. 2021 Aug 17;12:736670
pubmed: 34484246
J Immunother Cancer. 2015 Sep 15;3:43
pubmed: 26380088
Lancet. 2016 Apr 30;387(10030):1837-46
pubmed: 26970723
J Histochem Cytochem. 2017 Aug;65(8):431-444
pubmed: 28692376
Sci Transl Med. 2017 Apr 12;9(385):
pubmed: 28404865
Cell. 2019 Jun 13;177(7):1888-1902.e21
pubmed: 31178118
J Immunol. 1998 Sep 1;161(5):2457-64
pubmed: 9725244
Circ Res. 2018 Mar 2;122(5):670-677
pubmed: 29358229
Cell. 1996 Aug 23;86(4):643-53
pubmed: 8752218
Nat Commun. 2020 Jul 30;11(1):3798
pubmed: 32732867
Trends Immunol. 2015 Apr;36(4):240-9
pubmed: 25770923
Cancer Immunol Res. 2017 Nov;5(11):1005-1015
pubmed: 28947544
Cell Rep. 2015 Dec 29;13(12):2687-98
pubmed: 26711337
Nat Immunol. 2017 Nov;18(11):1207-1217
pubmed: 28892469
Nat Rev Immunol. 2010 Sep;10(9):664-74
pubmed: 20706277
Cancer Res. 2011 Sep 1;71(17):5678-87
pubmed: 21846823
Front Immunol. 2021 May 27;12:674375
pubmed: 34122434
J Cell Biol. 1988 Nov;107(5):1853-62
pubmed: 2460470
Nat Rev Immunol. 2012 Nov;12(11):762-73
pubmed: 23018291