β2-adrenergic receptor signaling regulates metabolic pathways critical to myeloid-derived suppressor cell function within the TME.
MDSCs
autophagy
cancer
fatty acid oxidation
immune suppression
metabolism
oxidative phosphorylation
prostaglandin E2
stress
β-adrenergic signaling
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
26 10 2021
26 10 2021
Historique:
received:
24
03
2021
revised:
11
08
2021
accepted:
01
10
2021
entrez:
27
10
2021
pubmed:
28
10
2021
medline:
11
2
2022
Statut:
ppublish
Résumé
Myeloid-derived suppressor cells (MDSCs) impede antitumor immunity; however, the precise mechanisms that regulate their suppressive function remain unresolved. Identifying these mechanisms could lead to therapeutic interventions to boost cancer immunotherapy efficacy. Here, we reveal that β2 adrenergic receptor (β2-AR) expression on MDSCs increases with tumor growth and that the β2-AR stress pathway drives the immune suppressive activity of MDSCs by altering their metabolism. We show that β2-AR signaling decreases glycolysis and increases oxidative phosphorylation and fatty acid oxidation (FAO). It also increases expression of the fatty acid transporter CPT1A, which is necessary for the FAO-mediated immunosuppressive function of MDSCs. Moreover, we show that β2-AR signaling increases autophagy and activates the arachidonic acid cycle, both required for increasing the release of the immunosuppressive mediator, PGE2. Our data reveal that β2-AR signaling triggered by stress is an important physiological regulator of key metabolic pathways in MDSCs, driving their immunosuppressive function.
Identifiants
pubmed: 34706232
pii: S2211-1247(21)01353-X
doi: 10.1016/j.celrep.2021.109883
pmc: PMC8601406
mid: NIHMS1752051
pii:
doi:
Substances chimiques
ADRB2 protein, mouse
0
Neoplasm Proteins
0
Receptors, Adrenergic, beta-2
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
109883Subventions
Organisme : NCI NIH HHS
ID : F32 CA239356
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016056
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA099326
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA205246
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA172105
Pays : United States
Organisme : NCI NIH HHS
ID : F30 CA265127
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA085183
Pays : United States
Organisme : NHLBI NIH HHS
ID : K99 HL155792
Pays : United States
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
Références
J Clin Invest. 2018 Jul 2;128(7):2732-2742
pubmed: 29733297
Cancer Immunol Res. 2021 Jun;9(6):651-664
pubmed: 33762351
J Leukoc Biol. 2016 Sep;100(3):463-70
pubmed: 26864266
Oncoimmunology. 2017 Dec 21;7(3):e1405205
pubmed: 29399407
Trends Immunol. 2015 Feb;36(2):81-91
pubmed: 25592731
J Invest Dermatol. 2015 May;135(5):1425-1434
pubmed: 25581502
Br J Cancer. 2019 Jan;120(1):16-25
pubmed: 30413826
Nat Immunol. 2018 Feb;19(2):108-119
pubmed: 29348500
Cell Death Dis. 2020 Sep 10;11(9):736
pubmed: 32913185
Nature. 2019 May;569(7754):73-78
pubmed: 30996346
Science. 2013 Jul 12;341(6142):1236361
pubmed: 23846904
Oxid Med Cell Longev. 2019 Nov 4;2019:3809308
pubmed: 31781334
Pharmacol Ther. 2007 Mar;113(3):523-36
pubmed: 17303246
Sci Immunol. 2020 Feb 21;5(44):
pubmed: 32086381
Cancer Res. 2007 May 1;67(9):4507-13
pubmed: 17483367
J Immunol. 2018 Jan 15;200(2):422-431
pubmed: 29311384
J Clin Invest. 2018 Aug 31;128(9):3840-3852
pubmed: 29920188
Semin Immunopathol. 2020 Dec;42(6):719-734
pubmed: 32948909
Clin J Oncol Nurs. 2020 Feb 1;24(1):51-57
pubmed: 31961831
Front Immunol. 2019 Mar 18;10:475
pubmed: 30936876
Front Immunol. 2019 Feb 04;10:115
pubmed: 30778354
Cancer Res. 2017 Oct 15;77(20):5639-5651
pubmed: 28819022
Br J Cancer. 2020 Jan;122(1):23-29
pubmed: 31819182
Immunity. 2015 Sep 15;43(3):435-49
pubmed: 26377897
Cell Metab. 2018 Jul 03;28(1):87-103.e6
pubmed: 29805099
Immunol Rev. 2018 May;283(1):213-231
pubmed: 29664569
Nat Rev Immunol. 2021 Aug;21(8):485-498
pubmed: 33526920
Cell Immunol. 2021 Apr;362:104297
pubmed: 33550187
Cell Stress. 2019 Jan 23;3(2):47-65
pubmed: 31225500
Proc Natl Acad Sci U S A. 2013 Sep 17;110(38):15289-94
pubmed: 24003153
Front Immunol. 2018 Mar 02;9:398
pubmed: 29552012
Cancer Immunol Immunother. 2019 Jan;68(1):11-22
pubmed: 30229289
Cell Metab. 2006 Jul;4(1):13-24
pubmed: 16814729
Cancer Immunol Res. 2015 Nov;3(11):1236-47
pubmed: 26025381
Semin Immunopathol. 2013 Mar;35(2):123-37
pubmed: 22996682
J Nutr Biochem. 2016 Aug;34:1-7
pubmed: 27424223
Clin Sci (Lond). 2007 Aug;113(4):205-12
pubmed: 17319797
Br J Cancer. 2020 Jan;122(1):4-22
pubmed: 31819192
Cancer Discov. 2019 Jun;9(6):702-710
pubmed: 30944117
Clin Cancer Res. 2021 Jan 1;27(1):87-95
pubmed: 33127652
FASEB J. 2019 May;33(5):5967-5978
pubmed: 30730772
Cell Death Dis. 2016 May 19;7:e2226
pubmed: 27195673
Neural Regen Res. 2019 Feb;14(2):280-288
pubmed: 30531011
Front Immunol. 2019 Feb 07;10:172
pubmed: 30792719
Front Immunol. 2020 Jul 22;11:1371
pubmed: 32793192
J Clin Invest. 2019 Dec 2;129(12):5537-5552
pubmed: 31566578
Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20176-81
pubmed: 24248371
Trends Immunol. 2016 Mar;37(3):208-220
pubmed: 26858199
Nat Commun. 2020 Aug 13;11(1):4056
pubmed: 32792483
BMC Cell Biol. 2012 Jul 04;13:18
pubmed: 22762146
Nucleic Acids Res. 2016 Jul 8;44(W1):W90-7
pubmed: 27141961
Front Immunol. 2019 Jun 19;10:1399
pubmed: 31275326
Nat Neurosci. 2019 Aug;22(8):1289-1305
pubmed: 31285612
Nat Immunol. 2010 Oct;11(10):889-96
pubmed: 20856220
Oncoimmunology. 2017 Jun 30;6(10):e1344804
pubmed: 29123954
J Leukoc Biol. 2010 Nov;88(5):839-48
pubmed: 20587738
Nat Commun. 2017 Apr 06;8:14979
pubmed: 28382931
J Leukoc Biol. 2010 Nov;88(5):827-9
pubmed: 21041513