Neutrophils in lung cancer patients: Activation potential and neutrophil extracellular trap formation.
cancer-associated thrombosis
high-density neutrophil
low-density neutrophil
lung cancer
neutrophil extracellular traps
Journal
Research and practice in thrombosis and haemostasis
ISSN: 2475-0379
Titre abrégé: Res Pract Thromb Haemost
Pays: United States
ID NLM: 101703775
Informations de publication
Date de publication:
Feb 2023
Feb 2023
Historique:
received:
05
08
2022
revised:
03
03
2023
accepted:
06
03
2023
medline:
18
4
2023
entrez:
17
4
2023
pubmed:
18
4
2023
Statut:
epublish
Résumé
Patients with cancer have an increased risk of developing venous thromboembolism. Neutrophils and neutrophil extracellular traps (NETs) reportedly influence the risk of cancer-associated thrombosis. Subpopulations of high and low-density neutrophils (HDN/LDN) are of specific interest, as they might have different functions in cancer patients. We aimed to investigate differences between HDNs and LDNs of patients with lung cancer and healthy controls, and their ability of activation and NET formation. Within the framework of the Vienna Cancer and Thrombosis Study, a prospective observational cohort study, HDNs and LDNs from 20 patients with lung cancer and 20 controls were isolated by density gradient centrifugation. The ability of neutrophil subpopulations for activation and NET formation was investigated by flow cytometry. Compared to controls, patients with cancer had higher numbers of total leukocytes, HDNs, and LDNs. LDNs of patients were more frequently in an activated state (CD62L↓/CD16↑) at baseline (median [IQR] 5.9% [3.4-8.8] vs 2.5% [1.6-6.7]). HDNs and LDNs from patients showed a significantly increased response to stimulation with ionomycin (CD11b HDN: 98.5 [95.4-99.4] vs 41.7 [13.4-91.6]; LDN: 82.9 [63-94] vs 39.6 [17.3-72.1]). In addition, HDNs from patients showed a higher capability of NET formation after ionomycin stimulation compared to HDNs from healthy controls (18509.5 [12242.5-29470.3] vs 10001 [6618.8-18384.3]). Protumorigenic LDNs were elevated, and neutrophil subpopulations showed an increased activation profile and ability for NET formation in patients with cancer. These mechanisms might be involved in tumor promotion and contribute to the prothrombotic phenotype of neutrophils in cancer.
Sections du résumé
Background
UNASSIGNED
Patients with cancer have an increased risk of developing venous thromboembolism. Neutrophils and neutrophil extracellular traps (NETs) reportedly influence the risk of cancer-associated thrombosis. Subpopulations of high and low-density neutrophils (HDN/LDN) are of specific interest, as they might have different functions in cancer patients.
Objectives
UNASSIGNED
We aimed to investigate differences between HDNs and LDNs of patients with lung cancer and healthy controls, and their ability of activation and NET formation.
Methods
UNASSIGNED
Within the framework of the Vienna Cancer and Thrombosis Study, a prospective observational cohort study, HDNs and LDNs from 20 patients with lung cancer and 20 controls were isolated by density gradient centrifugation. The ability of neutrophil subpopulations for activation and NET formation was investigated by flow cytometry.
Results
UNASSIGNED
Compared to controls, patients with cancer had higher numbers of total leukocytes, HDNs, and LDNs. LDNs of patients were more frequently in an activated state (CD62L↓/CD16↑) at baseline (median [IQR] 5.9% [3.4-8.8] vs 2.5% [1.6-6.7]). HDNs and LDNs from patients showed a significantly increased response to stimulation with ionomycin (CD11b HDN: 98.5 [95.4-99.4] vs 41.7 [13.4-91.6]; LDN: 82.9 [63-94] vs 39.6 [17.3-72.1]). In addition, HDNs from patients showed a higher capability of NET formation after ionomycin stimulation compared to HDNs from healthy controls (18509.5 [12242.5-29470.3] vs 10001 [6618.8-18384.3]).
Conclusion
UNASSIGNED
Protumorigenic LDNs were elevated, and neutrophil subpopulations showed an increased activation profile and ability for NET formation in patients with cancer. These mechanisms might be involved in tumor promotion and contribute to the prothrombotic phenotype of neutrophils in cancer.
Identifiants
pubmed: 37063752
doi: 10.1016/j.rpth.2023.100126
pii: S2475-0379(23)00097-3
pmc: PMC10099311
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100126Informations de copyright
© Bsc1 |.
Références
Immunol Rev. 2016 Sep;273(1):48-60
pubmed: 27558327
Arthritis Rheumatol. 2015 Nov;67(11):2990-3003
pubmed: 26097119
Cancer Res. 2001 Jun 15;61(12):4756-60
pubmed: 11406548
J Exp Med. 1995 Jan 1;181(1):435-40
pubmed: 7807024
Science. 2004 Mar 5;303(5663):1532-5
pubmed: 15001782
Cell Rep. 2015 Feb 3;10(4):562-73
pubmed: 25620698
FASEB J. 2020 Mar;34(3):4204-4218
pubmed: 31957112
Thromb Res. 2001 Jun 15;102(6):V215-24
pubmed: 11516455
Nat Rev Cancer. 2016 Jul;16(7):431-46
pubmed: 27282249
Blood. 2015 Jul 30;126(5):582-8
pubmed: 26109205
J Immunol. 2007 Dec 15;179(12):8454-62
pubmed: 18056392
J Immunol Res. 2015;2015:983698
pubmed: 26819959
Front Cell Infect Microbiol. 2017 May 29;7:217
pubmed: 28611952
Crit Care. 2003 Aug;7(4):291-307
pubmed: 12930553
Blood. 2014 May 1;123(18):2768-76
pubmed: 24366358
Clin Cancer Res. 2016 Jan 1;22(1):200-6
pubmed: 26302981
J Clin Invest. 1988 Mar;81(3):676-82
pubmed: 3278004
J Leukoc Biol. 2010 Jul;88(1):211-20
pubmed: 20400675
Haematologica. 2020 Jan;105(1):218-225
pubmed: 31048354
Front Immunol. 2018 Nov 09;9:2456
pubmed: 30473691
Immune Netw. 2017 Oct;17(5):298-306
pubmed: 29093651
Rheumatology (Oxford). 2021 Apr 6;60(4):1687-1699
pubmed: 33026085
Basic Res Cardiol. 2019 Jul 16;114(5):33
pubmed: 31312919
Blood. 2014 Jul 31;124(5):710-9
pubmed: 24923297
Blood. 2021 Apr 8;137(14):1959-1969
pubmed: 33171494
J Immunol. 2010 Mar 15;184(6):3284-97
pubmed: 20164424
J Thromb Haemost. 2003 Jul;1(7):1343-8
pubmed: 12871267
Cancers (Basel). 2020 Jun 18;12(6):
pubmed: 32570944
J Immunol. 2011 Jul 1;187(1):538-52
pubmed: 21613614
Oncologist. 2016 Feb;21(2):252-7
pubmed: 26764252
Cancer Immunol Immunother. 2020 Feb;69(2):199-213
pubmed: 31982939
Ann Hematol. 2017 Mar;96(3):489-495
pubmed: 28018998
Shock. 2006 Dec;26(6):558-64
pubmed: 17117129
Proc Natl Acad Sci U S A. 2012 Aug 7;109(32):13076-81
pubmed: 22826226
J Immunol. 1992 Sep 15;149(6):2163-71
pubmed: 1381398
J Leukoc Biol. 2017 Sep;102(3):685-688
pubmed: 28360185
Front Immunol. 2012 Nov 29;3:360
pubmed: 23264775
Semin Thromb Hemost. 2014 Apr;40(3):277-83
pubmed: 24590420
Carcinogenesis. 2012 May;33(5):949-55
pubmed: 22425643
Immunity. 2019 Jul 16;51(1):27-41
pubmed: 31315034
Br J Haematol. 2019 Jul;186(2):311-320
pubmed: 30968400
Immunobiology. 2017 Jan;222(1):82-88
pubmed: 26874580
Am J Pathol. 1998 Jan;152(1):83-92
pubmed: 9422526
Nature. 2020 Jul;583(7814):133-138
pubmed: 32528174
J Clin Invest. 2012 Jan;122(1):327-36
pubmed: 22156198
J Thromb Haemost. 2018 Mar;16(3):508-518
pubmed: 29325226
Nat Rev Dis Primers. 2022 Feb 17;8(1):11
pubmed: 35177631
J Cell Biol. 2007 Jan 15;176(2):231-41
pubmed: 17210947
Tumour Biol. 2016 Nov;37(11):14355-14361
pubmed: 27614687
Cancer Microenviron. 2015 Dec;8(3):125-58
pubmed: 24895166
Semin Immunopathol. 2013 Jul;35(4):455-63
pubmed: 23553215