Tumor Cell-Autonomous SHP2 Contributes to Immune Suppression in Metastatic Breast Cancer.
Journal
Cancer research communications
ISSN: 2767-9764
Titre abrégé: Cancer Res Commun
Pays: United States
ID NLM: 9918281580506676
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
15
03
2022
revised:
18
07
2022
accepted:
26
08
2022
entrez:
27
3
2023
pubmed:
28
3
2023
medline:
28
3
2023
Statut:
epublish
Résumé
SH2 containing protein tyrosine phosphatase-2 (SHP2) is recognized as a druggable oncogenic phosphatase that is expressed in both tumor cells and immune cells. How tumor cell-autonomous SHP2 contributes to an immunosuppressive tumor microenvironment (TME) and therapeutic failure of immune checkpoint blockades in metastatic breast cancer (MBC) is not fully understood. Herein, we utilized systemic SHP2 inhibition and inducible genetic depletion of SHP2 to investigate immune reprogramming during SHP2 targeting. Pharmacologic inhibition of SHP2 sensitized MBC cells growing in the lung to α-programmed death ligand 1 (α-PD-L1) antibody treatment via relieving T-cell exhaustion induced by checkpoint blockade. Tumor cell-specific depletion of SHP2 similarly reduced pulmonary metastasis and also relieved exhaustion markers on CD8 Findings present inhibition of SHP2 as a therapeutic option to limit breast cancer metastasis by promoting antitumor immunity.
Identifiants
pubmed: 36969745
doi: 10.1158/2767-9764.CRC-22-0117
pii: CRC-22-0117
pmc: PMC10035406
doi:
Substances chimiques
B7-H1 Antigen
0
Banques de données
ClinicalTrials.gov
['NCT04000529']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
1104-1118Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR002529
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA232589
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA207751
Pays : United States
Organisme : NCI NIH HHS
ID : F99 CA264734
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA069202
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA023168
Pays : United States
Informations de copyright
© 2022 The Authors; Published by the American Association for Cancer Research.
Déclaration de conflit d'intérêts
Z.-Y. Zhang reports grants from National Institutes of Health during the conduct of the study; personal fees from Tyligand Bioscience outside the submitted work. No other disclosures were reported.
Références
Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15016-21
pubmed: 18809920
Nature. 2016 Jul 7;535(7610):148-52
pubmed: 27362227
Cancer Immunol Res. 2020 Dec;8(12):1542-1553
pubmed: 33093218
Ann Oncol. 2019 Mar 1;30(3):405-411
pubmed: 30475947
Cancer Cell. 2020 Nov 9;38(5):685-700.e8
pubmed: 33007259
Nat Biotechnol. 2019 Jul;37(7):773-782
pubmed: 31061481
J Med Chem. 2016 Sep 8;59(17):7773-82
pubmed: 27347692
Oncogene. 2018 Sep;37(37):5088-5100
pubmed: 29795405
Nat Rev Drug Discov. 2018 Nov;17(11):783-784
pubmed: 30337722
Cell Rep. 2018 Apr 3;23(1):39-49
pubmed: 29617671
Oncotarget. 2016 Nov 8;7(45):73817-73829
pubmed: 27650545
Nat Commun. 2018 Oct 30;9(1):4508
pubmed: 30375388
Sci Rep. 2021 Jan 14;11(1):1399
pubmed: 33446805
Cancer Cell. 2016 Mar 14;29(3):285-296
pubmed: 26977880
Mol Cancer Res. 2018 Oct;16(10):1579-1589
pubmed: 29934326
Lancet Oncol. 2019 Mar;20(3):e175-e186
pubmed: 30842061
Sci Rep. 2020 Oct 28;10(1):18530
pubmed: 33116231
Am Health Drug Benefits. 2016 Feb;9(1):23-32
pubmed: 27066193
Oncogene. 2021 Jan;40(2):322-333
pubmed: 33128042
Nat Commun. 2021 Nov 2;12(1):6310
pubmed: 34728626
JNCI Cancer Spectr. 2021 Jul 13;5(4):
pubmed: 34409255
Curr Protoc Immunol. 2001 May;Chapter 20:Unit 20.2
pubmed: 18432775
Oncogene. 2020 Dec;39(49):7166-7180
pubmed: 33033382
Breast Cancer Res Treat. 2022 Jan;191(1):15-29
pubmed: 34623509
Nat Med. 2012 Mar 04;18(4):529-37
pubmed: 22388088
Cancer Immunol Res. 2020 Jul;8(7):883-894
pubmed: 32299915
Front Mol Biosci. 2021 Jul 09;8:679130
pubmed: 34307450
Nat Methods. 2015 May;12(5):453-7
pubmed: 25822800
J Exp Med. 2021 Jan 4;218(1):
pubmed: 33045063
Acta Pharm Sin B. 2022 Jan;12(1):149-166
pubmed: 35127377
Cancer Lett. 2020 Feb 1;470:126-133
pubmed: 31730903
Science. 2017 Mar 31;355(6332):1428-1433
pubmed: 28280247
Cancer Res. 2020 Jul 1;80(13):2889-2902
pubmed: 32350067
Leukemia. 2017 Jun;31(6):1415-1422
pubmed: 27840422
Pharmacol Res. 2020 Feb;152:104595
pubmed: 31838080
CA Cancer J Clin. 2021 Jan;71(1):7-33
pubmed: 33433946
Clin Cancer Res. 2011 Oct 1;17(19):6118-24
pubmed: 21705455
Vaccines (Basel). 2019 Oct 12;7(4):
pubmed: 31614877
J Med Chem. 2020 Nov 25;63(22):13578-13594
pubmed: 32910655
Sci Adv. 2020 Jan 31;6(5):eaay4458
pubmed: 32064351
Nat Genet. 2003 Jul;34(3):267-73
pubmed: 12808457
Clin Cancer Res. 2020 Jul 1;26(13):3333-3344
pubmed: 32299814
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Cancers (Basel). 2021 Aug 26;13(17):
pubmed: 34503119
J Cell Mol Med. 2015 Sep;19(9):2075-83
pubmed: 26088100
Cell. 1998 Feb 20;92(4):441-50
pubmed: 9491886
Nat Med. 2018 Jul;24(7):954-960
pubmed: 29808009
Nat Commun. 2015 Nov 30;6:8859
pubmed: 26617336
Breast Cancer Res. 2009;11(5):R68
pubmed: 19740433
Curr Opin Immunol. 1999 Feb;11(1):76-81
pubmed: 10047537
Cell Death Dis. 2018 Sep 24;9(10):976
pubmed: 30250119
Clin Cancer Res. 2021 Jan 1;27(1):342-354
pubmed: 33046519
Breast Cancer Res. 2016 Jan 04;18(1):2
pubmed: 26728598
J Exp Med. 2012 Jun 4;209(6):1201-17
pubmed: 22641383
Adv Mater. 2019 Dec;31(51):e1904364
pubmed: 31659802
JCI Insight. 2018 Jun 7;3(11):
pubmed: 29875321
Clin Cancer Res. 2021 Apr 15;27(8):2168-2178
pubmed: 33514524
Trends Immunol. 2006 Mar;27(3):154-60
pubmed: 16458607
Cell Rep. 2015 Sep 29;12(12):1978-85
pubmed: 26365186
Clin Cancer Res. 2018 Nov 1;24(21):5368-5380
pubmed: 30042205
J Immunol. 2014 Sep 15;193(6):2801-11
pubmed: 25127857
Nat Med. 2018 Jul;24(7):961-967
pubmed: 29808006
Mol Cell Biol. 2003 Nov;23(21):7875-86
pubmed: 14560030
Commun Biol. 2020 Mar 17;3(1):128
pubmed: 32184441
N Engl J Med. 2020 Feb 27;382(9):810-821
pubmed: 32101663
Nat Commun. 2013;4:2612
pubmed: 24113773
Mol Cancer Ther. 2016 Sep;15(9):2096-106
pubmed: 27371729
Acta Pharm Sin B. 2019 Mar;9(2):304-315
pubmed: 30972278
Cancer Immunol Res. 2019 Feb;7(2):193-207
pubmed: 30514794
Methods Mol Biol. 2020;2120:223-232
pubmed: 32124323