β3-adrenergic receptor on tumor-infiltrating lymphocytes sustains IFN-γ-dependent PD-L1 expression and impairs anti-tumor immunity in neuroblastoma.
Journal
Cancer gene therapy
ISSN: 1476-5500
Titre abrégé: Cancer Gene Ther
Pays: England
ID NLM: 9432230
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
09
08
2022
accepted:
09
02
2023
revised:
27
01
2023
medline:
22
6
2023
pubmed:
2
3
2023
entrez:
1
3
2023
Statut:
ppublish
Résumé
Neuroblastoma (NB) is a heterogeneous extracranial tumor occurring in childhood. A distinctive feature of NB tumors is their neuroendocrine ability to secrete catecholamines, which in turn, via β-adrenergic receptors ligation, may affect different signaling pathways in tumor microenvironment (TME). It was previously demonstrated that specific antagonism of β3-adrenergic receptor (β3-AR) on NB tumor cells affected tumor growth and progression. Here, in a murine syngeneic model of NB, we aimed to investigate whether the β3-AR modulation influenced the host immune system response against tumor. Results demonstrated that β3-AR antagonism lead to an immune response reactivation, partially dependent on the PD-1/PD-L1 signaling axis involvement. Indeed, β3-AR blockade on tumor-infiltrating lymphocytes (TILs) dampened their ability to secrete IFN-γ, which in turn reduced the PD-L1 expression, caused by TILs infiltration, on NB tumor cells. Further investigations, through a genomic analysis on NB patients, showed that high ADRB3 gene expression correlates with worse clinical outcome compared to the low expression group, and that ADRB3 gene expression affects different immune-related pathways. Overall, results indicate that β3-AR in NB TME is able to modulate the interaction between tumor and host immune system, and that its antagonism hits multiple pro-tumoral signaling pathways.
Identifiants
pubmed: 36854895
doi: 10.1038/s41417-023-00599-x
pii: 10.1038/s41417-023-00599-x
pmc: PMC10281870
doi:
Substances chimiques
Interferon-gamma
82115-62-6
B7-H1 Antigen
0
Receptors, Adrenergic, beta-3
0
ADRB3 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
890-904Informations de copyright
© 2023. The Author(s).
Références
Pediatr Blood Cancer. 2007 May;48(5):504-9
pubmed: 16732582
Cancer Res. 2009 Oct 15;69(20):8067-75
pubmed: 19826049
Mol Cell. 2019 Nov 7;76(3):359-370
pubmed: 31668929
J Exp Med. 2009 Jun 8;206(6):1327-37
pubmed: 19451266
Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14733-8
pubmed: 20679213
J Immunol. 2008 Aug 1;181(3):2056-64
pubmed: 18641343
Oncoscience. 2017 Aug 23;4(7-8):95-105
pubmed: 28966942
Cancer. 2017 Oct 1;123(19):3807-3815
pubmed: 28608950
Oncoimmunology. 2021 Jan 4;10(1):1838140
pubmed: 33489468
Oncoimmunology. 2015 Apr 2;4(9):e1019981
pubmed: 26405592
Pediatr Surg Int. 2020 Feb;36(2):137-143
pubmed: 31925505
Oncotarget. 2017 Jan 24;8(4):6446-6460
pubmed: 28031536
Science. 2013 Jul 12;341(6142):1236361
pubmed: 23846904
Nat Immunol. 2009 Jan;10(1):29-37
pubmed: 19043418
Exp Mol Med. 2018 Dec 13;50(12):1-11
pubmed: 30546008
Brain Behav Immun. 1997 Dec;11(4):286-306
pubmed: 9512816
J Immunother Cancer. 2021 Apr;9(4):
pubmed: 33795387
Br J Pharmacol. 2019 Jul;176(14):2509-2524
pubmed: 30874296
Cells. 2019 Apr 16;8(4):
pubmed: 30995798
Sci Transl Med. 2019 Feb 13;11(479):
pubmed: 30760579
Breast Cancer Res. 2001;3(4):264-9
pubmed: 11434877
Exp Cell Res. 1997 Apr 10;232(1):25-8
pubmed: 9141617
Science. 2006 Sep 29;313(5795):1960-4
pubmed: 17008531
Pediatr Blood Cancer. 2013 Sep;60(9):1418-23
pubmed: 23704073
Front Immunol. 2017 Aug 10;8:961
pubmed: 28848559
Int Immunol. 1996 May;8(5):765-72
pubmed: 8671665
Annu Rev Immunol. 2008;26:677-704
pubmed: 18173375
Oncology. 2008;75(3-4):224-9
pubmed: 18852493
Brain Behav Immun. 2002 Dec;16(6):785-98
pubmed: 12480507
J Clin Invest. 2007 Apr;117(4):871-3
pubmed: 17404615
Front Immunol. 2018 Feb 06;9:164
pubmed: 29479349
Eur J Cancer. 2017 Feb;72:235-243
pubmed: 28061374
J Exp Med. 2000 Oct 2;192(7):1027-34
pubmed: 11015443
Nat Commun. 2020 Nov 25;11(1):5992
pubmed: 33239635
Sci Rep. 2017 Oct 25;7(1):14049
pubmed: 29070883
J Clin Invest. 2014 May;124(5):2246-59
pubmed: 24667641
Nat Med. 2003 May;9(5):562-7
pubmed: 12704383
Biomark Res. 2020 Sep 29;8:49
pubmed: 33005420
Oncoimmunology. 2015 Jul 15;5(1):e1064578
pubmed: 26942080
Clin Cancer Res. 2012 Mar 1;18(5):1201-6
pubmed: 22186256
Nat Rev Cancer. 2013 Jun;13(6):397-411
pubmed: 23702928
J Exp Clin Cancer Res. 2004 Dec;23(4):669-74
pubmed: 15743038
Cancer Immunol Immunother. 2014 Nov;63(11):1115-28
pubmed: 25307152
Nat Rev Dis Primers. 2016 Nov 10;2:16078
pubmed: 27830764
PLoS Med. 2018 Jan 29;15(1):e1002497
pubmed: 29377881
Br J Pharmacol. 2019 Jul;176(14):2539-2558
pubmed: 30809805
J Mol Med (Berl). 2013 Dec;91(12):1407-19
pubmed: 23907236
Oncogene. 2020 Jan;39(2):368-384
pubmed: 31477835
Clin Vaccine Immunol. 2010 Sep;17(9):1377-80
pubmed: 20685939
Nat Rev Cancer. 2012 Mar 22;12(4):252-64
pubmed: 22437870
Mod Pathol. 2012 Nov;25(11):1446-51
pubmed: 22743651
Nature. 2004 Jan 22;427(6972):355-60
pubmed: 14737169
J Exp Med. 2010 Sep 27;207(10):2187-94
pubmed: 20819927
Nat Commun. 2020 Sep 24;11(1):4835
pubmed: 32973173
Sci Transl Med. 2016 Mar 2;8(328):328rv4
pubmed: 26936508
Ann Oncol. 2018 Jan 1;29(1):71-83
pubmed: 29069302
Cancer Cell. 2020 Nov 9;38(5):685-700.e8
pubmed: 33007259
Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12640-5
pubmed: 15314238
Semin Immunol. 2019 Jun;43:101280
pubmed: 31221552