Distinctive germline expression of class I human leukocyte antigen (HLA) alleles and DRB1 heterozygosis predict the outcome of patients with non-small cell lung cancer receiving PD-1/PD-L1 immune checkpoint blockade.
B7-H1 antigen
antigen presentation
lung neoplasms
tumor biomarkers
Journal
Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
accepted:
05
05
2020
entrez:
20
6
2020
pubmed:
20
6
2020
medline:
21
8
2021
Statut:
ppublish
Résumé
Nivolumab is a human monoclonal antibody against programmed cell death receptor-1 (PD-1) able to rescue quiescent tumor infiltrating cytotoxic T lymphocytes (CTLs) restoring their ability to kill target cells expressing specific tumor antigen-derived epitope peptides bound to homologue human leukocyte antigen (HLA) molecules. Nivolumab is currently an active but expensive therapeutic agent for metastatic non-small cell lung cancer (mNSCLC), producing, in some cases, immune-related adverse events (irAEs). At the present, no reliable biomarkers have been validated to predict either treatment response or adverse events in treated patients. We performed a retrospective multi-institutional analysis including 119 patients with mNSCLC who received PD-1 blockade since November 2015 to investigate the predictive role of germinal class I HLA and DRB1 genotype. We investigated the correlation among patients' outcome and irAEs frequency with specific HLA A, B, C and DRB1 alleles by reverse sequence-specific oligonucleotide (SSO) DNA typing. A poor outcome in patients negative for the expression of two most frequent HLA-A alleles was detected (HLA: HLA-A*01 and or A*02; progression-free survival (PFS): 7.5 (2.8 to 12.2) vs 15.9 (0 to 39.2) months, p=0.01). In particular, HLA-A*01-positive patients showed a prolonged PFS of 22.6 (10.2 to 35.0) and overall survival (OS) of 30.8 (7.7 to 53.9) months, respectively. We also reported that HLA-A and DRB1 locus heterozygosis (het) were correlated to a worse OS if we considered het in the locus A; in reverse, long survival was correlated to het in DRB1. This study demonstrate that class I and II HLA allele characterization to define tumor immunogenicity has relevant implications in predicting nivolumab efficacy in mNSCLC and provide the rationale for further prospective trials of cancer immunotherapy.
Sections du résumé
BACKGROUND
Nivolumab is a human monoclonal antibody against programmed cell death receptor-1 (PD-1) able to rescue quiescent tumor infiltrating cytotoxic T lymphocytes (CTLs) restoring their ability to kill target cells expressing specific tumor antigen-derived epitope peptides bound to homologue human leukocyte antigen (HLA) molecules. Nivolumab is currently an active but expensive therapeutic agent for metastatic non-small cell lung cancer (mNSCLC), producing, in some cases, immune-related adverse events (irAEs). At the present, no reliable biomarkers have been validated to predict either treatment response or adverse events in treated patients.
METHODS
We performed a retrospective multi-institutional analysis including 119 patients with mNSCLC who received PD-1 blockade since November 2015 to investigate the predictive role of germinal class I HLA and DRB1 genotype. We investigated the correlation among patients' outcome and irAEs frequency with specific HLA A, B, C and DRB1 alleles by reverse sequence-specific oligonucleotide (SSO) DNA typing.
RESULTS
A poor outcome in patients negative for the expression of two most frequent HLA-A alleles was detected (HLA: HLA-A*01 and or A*02; progression-free survival (PFS): 7.5 (2.8 to 12.2) vs 15.9 (0 to 39.2) months, p=0.01). In particular, HLA-A*01-positive patients showed a prolonged PFS of 22.6 (10.2 to 35.0) and overall survival (OS) of 30.8 (7.7 to 53.9) months, respectively. We also reported that HLA-A and DRB1 locus heterozygosis (het) were correlated to a worse OS if we considered het in the locus A; in reverse, long survival was correlated to het in DRB1.
CONCLUSIONS
This study demonstrate that class I and II HLA allele characterization to define tumor immunogenicity has relevant implications in predicting nivolumab efficacy in mNSCLC and provide the rationale for further prospective trials of cancer immunotherapy.
Identifiants
pubmed: 32554614
pii: jitc-2020-000733
doi: 10.1136/jitc-2020-000733
pmc: PMC7304840
pii:
doi:
Substances chimiques
HLA Antigens
0
Immune Checkpoint Inhibitors
0
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
Références
J Clin Oncol. 2017 Dec 10;35(35):3924-3933
pubmed: 29023213
J Clin Oncol. 2015 Jun 20;33(18):2092-9
pubmed: 25918278
Arthritis Rheum. 1987 Nov;30(11):1205-13
pubmed: 2446635
Br Med Bull. 2005 Feb 08;71:93-113
pubmed: 15701924
Thorax. 2015 Apr;70(4):359-67
pubmed: 25661113
Lancet Oncol. 2017 Mar;18(3):e143-e152
pubmed: 28271869
Nature. 1991 May 23;351(6324):290-6
pubmed: 1709722
Tissue Antigens. 2014 May;83(5):307-23
pubmed: 24738646
Lancet. 2017 Jan 21;389(10066):299-311
pubmed: 27574741
Cancer Immunol Immunother. 2015 Sep;64(9):1159-73
pubmed: 26031574
Clin Dev Immunol. 2010;2010:539519
pubmed: 20976125
Science. 2018 Feb 2;359(6375):582-587
pubmed: 29217585
Lung Cancer. 2019 Aug;134:245-253
pubmed: 31319988
Nat Rev Cancer. 2016 May;16(5):275-87
pubmed: 27079802
Hum Vaccin Immunother. 2014;10(11):3175-8
pubmed: 25483658
Ann Oncol. 2012 Feb;23(2):442-9
pubmed: 21873272
Endocr Metab Immune Disord Drug Targets. 2007 Jun;7(2):99-109
pubmed: 17584150
J Immunother Cancer. 2019 Nov 15;7(1):306
pubmed: 31730012
J Clin Oncol. 2005 Sep 1;23(25):6043-53
pubmed: 16087944
Immunotherapy. 2016 Nov;8(11):1281-1292
pubmed: 27993089
Clin Cancer Res. 2011 May 1;17(9):2668-78
pubmed: 21248298
Science. 1992 Mar 6;255(5049):1261-3
pubmed: 1546328
J Autoimmun. 2018 Dec;95:77-99
pubmed: 30174217
N Engl J Med. 2016 Dec 8;375(23):2255-2262
pubmed: 27959684
Methods Mol Biol. 2020;2055:325-350
pubmed: 31502159
Nat Med. 2019 Nov;25(11):1715-1720
pubmed: 31700181
J Immunol. 1991 Mar 1;146(5):1692-9
pubmed: 1671580
J Exp Med. 1989 Sep 1;170(3):797-810
pubmed: 2788708
J Immunol. 1994 Jan 1;152(1):163-75
pubmed: 8254189
Immunogenetics. 1999 Nov;50(3-4):213-9
pubmed: 10602881
Mol Clin Oncol. 2019 Jul;11(1):81-90
pubmed: 31289683
Mol Cell Proteomics. 2019 Aug;18(8):1491-1510
pubmed: 31092671
J Natl Cancer Inst. 1997 Feb 19;89(4):293-300
pubmed: 9048833
J Thorac Oncol. 2019 Jun;14(6):1021-1031
pubmed: 30780001
Oncotarget. 2018 Apr 17;9(29):20539-20554
pubmed: 29755670
Clin Cancer Res. 2019 May 15;25(10):3026-3034
pubmed: 30765392
J Immunol. 2013 Jan 15;190(2):513-8
pubmed: 23293357
Nat Rev Cancer. 2012 Mar 22;12(4):252-64
pubmed: 22437870
Oncoimmunology. 2015 Dec 21;5(4):e1101205
pubmed: 27141384
Oncologist. 2019 Feb;24(Suppl 1):S31-S41
pubmed: 30819829
BioDrugs. 2016 Dec;30(6):571-584
pubmed: 27848165
Clin Cancer Res. 1997 Dec;3(12 Pt 1):2439-49
pubmed: 9815645