Peroxynitrite in the tumor microenvironment changes the profile of antigens allowing escape from cancer immunotherapy.
cancer immunotherapy
cytotoxic T cells
myeloid cells
peroxynitrite
tumor microenvironment
tumor-associated antigens
Journal
Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617
Informations de publication
Date de publication:
10 10 2022
10 10 2022
Historique:
received:
05
10
2021
revised:
12
06
2022
accepted:
31
08
2022
entrez:
11
10
2022
pubmed:
12
10
2022
medline:
14
10
2022
Statut:
ppublish
Résumé
Cancer immunotherapy often depends on recognition of peptide epitopes by cytotoxic T lymphocytes (CTLs). The tumor microenvironment (TME) is enriched for peroxynitrite (PNT), a potent oxidant produced by infiltrating myeloid cells and some tumor cells. We demonstrate that PNT alters the profile of MHC class I bound peptides presented on tumor cells. Only CTLs specific for PNT-resistant peptides have a strong antitumor effect in vivo, whereas CTLs specific for PNT-sensitive peptides are not effective. Therapeutic targeting of PNT in mice reduces resistance of tumor cells to CTLs. Melanoma patients with low PNT activity in their tumors demonstrate a better clinical response to immunotherapy than patients with high PNT activity. Our data suggest that intratumoral PNT activity should be considered for the design of neoantigen-based therapy and also may be an important immunotherapeutic target.
Identifiants
pubmed: 36220073
pii: S1535-6108(22)00393-2
doi: 10.1016/j.ccell.2022.09.001
pmc: PMC9566605
mid: NIHMS1835737
pii:
doi:
Substances chimiques
Antigens, Neoplasm
0
Epitopes
0
Histocompatibility Antigens Class I
0
Oxidants
0
Peptides
0
Peroxynitrous Acid
14691-52-2
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
1173-1189.e6Subventions
Organisme : NCI NIH HHS
ID : R01 CA165065
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE028172
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA174523
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016520
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA221838
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA010815
Pays : United States
Organisme : NCI NIH HHS
ID : R03 CA219603
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA114046
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA177646
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA261608
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests E.C. is a paid consultant for Oncovir, Inc. E.M., Q.Z., A.M., and D.I.G. are employees and shareholders of AstraZeneca.
Références
Redox Biol. 2018 Apr;14:618-625
pubmed: 29154193
J Immunol. 1999 Oct 15;163(8):4413-20
pubmed: 10510382
Int J Cancer. 2006 Aug 15;119(4):861-6
pubmed: 16557582
Cancer Inform. 2014 Dec 09;13(Suppl 4):65-72
pubmed: 25574127
Nat Med. 2018 May;24(5):541-550
pubmed: 29686425
Cell. 2012 Feb 17;148(4):727-38
pubmed: 22341445
Sci Data. 2018 Aug 07;5:180157
pubmed: 30084848
Hepatology. 2004 Sep;40(3):574-82
pubmed: 15349895
J Biol Chem. 2002 Feb 1;277(5):3614-21
pubmed: 11723112
Nat Med. 2007 Jul;13(7):828-35
pubmed: 17603493
Nature. 2019 Jan;565(7738):234-239
pubmed: 30568305
Free Radic Biol Med. 2011 Mar 15;50(6):749-62
pubmed: 21172423
Lancet. 2015 Feb 7;385(9967):517-528
pubmed: 25319501
Clin Cancer Res. 2006 Feb 15;12(4):1201-7
pubmed: 16489074
Cell Mol Life Sci. 2011 May;68(9):1491-502
pubmed: 21387144
Nature. 2017 Jul 13;547(7662):217-221
pubmed: 28678778
Cancer Res. 2012 Apr 15;72(8):1986-95
pubmed: 22367213
Cancer Immunol Immunother. 2019 May;68(5):773-785
pubmed: 30747243
Nature. 2014 Nov 27;515(7528):572-6
pubmed: 25428506
Clin Cancer Res. 2000 Dec;6(12):4768-75
pubmed: 11156233
J Clin Invest. 2005 Mar;115(3):739-46
pubmed: 15696196
Cancer Res. 2001 Jun 15;61(12):4756-60
pubmed: 11406548
J Exp Med. 1995 May 1;181(5):1881-6
pubmed: 7722462
Clin Cancer Res. 2012 Dec 15;18(24):6758-70
pubmed: 23032743
Am J Respir Cell Mol Biol. 2004 Aug;31(2):147-53
pubmed: 15039138
Nat Biotechnol. 2008 Dec;26(12):1367-72
pubmed: 19029910
Proc Int Conf Intell Syst Mol Biol. 1994;2:28-36
pubmed: 7584402
Transfus Med Rev. 2020 Jan;34(1):29-33
pubmed: 31677848
Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):4185-90
pubmed: 15753302
Methods Enzymol. 2008;441:283-94
pubmed: 18554540
Clin Cancer Res. 2010 Mar 15;16(6):1812-23
pubmed: 20215551
Nat Immunol. 2018 Feb;19(2):108-119
pubmed: 29348500
Mol Cell Proteomics. 2006 Feb;5(2):357-65
pubmed: 16272561
Arch Biochem Biophys. 1999 Nov 15;371(2):169-78
pubmed: 10545203
PLoS One. 2015 Apr 21;10(4):e0122942
pubmed: 25897966
J Clin Invest. 2011 Oct;121(10):4015-29
pubmed: 21911941
Prog Mol Biol Transl Sci. 2012;109:75-112
pubmed: 22727420
Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3849-54
pubmed: 18319339
Elife. 2017 Nov 28;6:
pubmed: 29182146
Front Immunol. 2018 Jul 05;9:1538
pubmed: 30026743
Mol Cell Proteomics. 2013 Jul;12(7):1853-64
pubmed: 23538226
Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13119-24
pubmed: 8917554
Biochem Pharmacol. 2015 Jul 1;96(1):1-9
pubmed: 25935605
Nat Rev Immunol. 2012 Mar 22;12(4):253-68
pubmed: 22437938