Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
20 07 2023
20 07 2023
Historique:
received:
14
05
2021
accepted:
09
06
2023
medline:
24
7
2023
pubmed:
21
7
2023
entrez:
20
7
2023
Statut:
epublish
Résumé
Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don't respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy. Based on in vitro pharmacological studies, mouse models and analyses of human melanoma patients, we show that the cytokine GDF-15 impairs LFA-1/β2-integrin-mediated adhesion of T cells to activated endothelial cells, which is a pre-requisite of T cell extravasation. In melanoma patients, GDF-15 serum levels strongly correlate with failure of PD-1-based immune checkpoint blockade therapy. Neutralization of GDF-15 improves both T cell trafficking and therapy efficiency in murine tumor models. Thus GDF-15, beside its known role in cancer-related anorexia and cachexia, emerges as a regulator of T cell extravasation into the tumor microenvironment, which provides an even stronger rationale for therapeutic anti-GDF-15 antibody development.
Identifiants
pubmed: 37474523
doi: 10.1038/s41467-023-39817-3
pii: 10.1038/s41467-023-39817-3
pmc: PMC10359308
doi:
Substances chimiques
Lymphocyte Function-Associated Antigen-1
0
Immune Checkpoint Inhibitors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4253Informations de copyright
© 2023. The Author(s).
Références
Cancer. 2006 Sep 15;107(6):1331-9
pubmed: 16909413
J Biol Chem. 2018 Aug 10;293(32):12318-12330
pubmed: 29903913
Nat Med. 2019 Aug;25(8):1251-1259
pubmed: 31359002
Cell. 2018 Nov 1;175(4):984-997.e24
pubmed: 30388455
J Immunother Cancer. 2021 Sep;9(9):
pubmed: 34489334
PLoS One. 2013 Nov 13;8(11):e78618
pubmed: 24236027
Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3410-5
pubmed: 12624183
Cell Rep. 2018 Feb 6;22(6):1522-1530
pubmed: 29425507
PLoS One. 2014 Mar 19;9(3):e92311
pubmed: 24647424
Cancer Cell. 2017 May 8;31(5):711-723.e4
pubmed: 28486109
Nat Immunol. 2016 Sep;17(9):1118-27
pubmed: 27400148
J Clin Invest. 2022 Jul 1;132(13):
pubmed: 35552271
Nature. 2019 Jul;571(7764):270-274
pubmed: 31207604
Genomics Proteomics Bioinformatics. 2016 Feb;14(1):55-61
pubmed: 26829645
Trends Immunol. 2019 Jun;40(6):472-481
pubmed: 31006548
Front Immunol. 2018 Oct 30;9:2407
pubmed: 30425709
Eur J Cancer. 2009 Jan;45(2):228-47
pubmed: 19097774
J Invest Dermatol. 2016 Dec;136(12):2444-2452
pubmed: 27705749
Nat Immunol. 2013 Apr;14(4):356-63
pubmed: 23475183
Cancer Immunol Immunother. 2016 Apr;65(4):393-403
pubmed: 26899388
Clin Cancer Res. 2016 Nov 15;22(22):5487-5496
pubmed: 27185375
Proc Natl Acad Sci U S A. 2016 Nov 29;113(48):E7759-E7768
pubmed: 27837020
Clin Cancer Res. 2003 Jul;9(7):2642-50
pubmed: 12855642
Clin Cancer Res. 2010 Aug 1;16(15):3851-9
pubmed: 20534737
Nat Protoc. 2011 Jun 16;6(7):991-1009
pubmed: 21720313
Clin Chem. 2017 Jan;63(1):140-151
pubmed: 28062617
Nat Methods. 2012 Nov;9(11):1040-1
pubmed: 23132113
Nat Metab. 2021 Apr;3(4):513-522
pubmed: 33846641
Oncotarget. 2017 Jul 4;8(27):44418-44433
pubmed: 28574843
Nat Med. 2011 May;17(5):581-8
pubmed: 21516086
Sci Immunol. 2022 Apr;7(70):eabk1692
pubmed: 35363540
Immunology. 1993 Feb;78(2):237-43
pubmed: 8097182
J Neurosci. 2009 Oct 28;29(43):13640-8
pubmed: 19864576
Lancet. 2004 Jan 10;363(9403):129-30
pubmed: 14726168
PLoS One. 2017 Nov 21;12(11):e0187349
pubmed: 29161287
Nat Med. 2017 Oct;23(10):1215-1219
pubmed: 28846098
Nat Med. 2018 Oct;24(10):1550-1558
pubmed: 30127393
Nat Commun. 2016 Oct 10;7:13119
pubmed: 27721490
J Exp Med. 1996 Apr 1;183(4):1415-26
pubmed: 8666900
Nature. 1986 Sep 18-24;323(6085):262-4
pubmed: 3093887
Nature. 2018 Feb 22;554(7693):538-543
pubmed: 29443964
Biol Reprod. 2012 Nov 29;87(5):125
pubmed: 22954796
Nature. 2014 Nov 27;515(7528):568-71
pubmed: 25428505
J Cachexia Sarcopenia Muscle. 2015 Dec;6(4):317-24
pubmed: 26672741
Clin Cancer Res. 2020 Sep 15;26(18):4842-4851
pubmed: 32586938
Oncotarget. 2015 Dec 1;6(38):40836-49
pubmed: 26517811
J Struct Biol. 2013 Oct;184(1):21-32
pubmed: 23726984
J Clin Invest. 2017 Oct 2;127(10):3796-3809
pubmed: 28891811
Clin Cancer Res. 2018 Feb 1;24(3):634-647
pubmed: 29018052
J Immunol. 2005 Feb 15;174(4):1820-9
pubmed: 15699108
Cell. 1987 Dec 4;51(5):813-9
pubmed: 3315233
Nat Commun. 2020 Apr 28;11(1):2054
pubmed: 32345968
Gene. 1999 Sep 3;237(1):105-11
pubmed: 10524241
Cancers (Basel). 2021 Sep 15;13(18):
pubmed: 34572844
Cell Metab. 2020 Dec 1;32(6):938-950.e6
pubmed: 33207247
Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11514-9
pubmed: 9326641
Front Immunol. 2020 Sep 10;11:2105
pubmed: 33013886
Prostate. 2015 Feb 15;75(3):255-65
pubmed: 25327758
Nat Commun. 2019 Jul 17;10(1):3137
pubmed: 31316055
J Clin Oncol. 2009 Dec 20;27(36):6199-206
pubmed: 19917835
PLoS One. 2016 Sep 09;11(9):e0161779
pubmed: 27610613
Aging Cell. 2010 Dec;9(6):1057-64
pubmed: 20854422
Nat Med. 2017 Oct;23(10):1150-1157
pubmed: 28846097
Nat Med. 2017 Oct;23(10):1158-1166
pubmed: 28846099
Science. 1999 Jul 9;285(5425):221-7
pubmed: 10398592
Nat Med. 2007 Nov;13(11):1333-40
pubmed: 17982462
EMBO J. 1989 Dec 1;8(12):3759-65
pubmed: 2479549
Bioengineered. 2022 Apr;13(4):9687-9707
pubmed: 35420978