Human G-MDSCs are neutrophils at distinct maturation stages promoting tumor growth in breast cancer.
Adult
Aged
Breast Neoplasms
/ immunology
Female
Gene Expression
/ genetics
Gene Expression Profiling
/ methods
Gene Expression Regulation, Neoplastic
/ genetics
Granulocytes
/ metabolism
Humans
Immunotherapy
/ methods
Melanoma
/ metabolism
Middle Aged
Myeloid Cells
/ metabolism
Myeloid-Derived Suppressor Cells
/ metabolism
Neutrophils
/ metabolism
Transcriptome
/ genetics
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
25
08
2020
revised:
10
09
2020
accepted:
10
09
2020
entrez:
22
9
2020
pubmed:
23
9
2020
medline:
17
7
2021
Statut:
epublish
Résumé
Myeloid-derived suppressor cells (MDSCs) are known to contribute to immune evasion in cancer. However, the function of the human granulocytic (G)-MDSC subset during tumor progression is largely unknown, and there are no established markers for their identification in human tumor specimens. Using gene expression profiling, mass cytometry, and tumor microarrays, we here demonstrate that human G-MDSCs occur as neutrophils at distinct maturation stages, with a disease-specific profile. G-MDSCs derived from patients with metastatic breast cancer and malignant melanoma display a unique immature neutrophil profile, that is more similar to healthy donor neutrophils than to G-MDSCs from sepsis patients. Finally, we show that primary G-MDSCs from metastatic breast cancer patients co-transplanted with breast cancer cells, promote tumor growth, and affect vessel formation, leading to myeloid immune cell exclusion. Our findings reveal a role for human G-MDSC in tumor progression and have clinical implications also for targeted immunotherapy.
Identifiants
pubmed: 32958605
pii: 3/11/e202000893
doi: 10.26508/lsa.202000893
pmc: PMC7536824
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2020 Mehmeti-Ajradini et al.
Références
Nat Commun. 2016 Oct 11;7:13050
pubmed: 27725631
Int J Mol Sci. 2017 Aug 03;18(8):
pubmed: 28771176
Immune Netw. 2018 Jan 25;18(1):e5
pubmed: 29503738
Annu Rev Pathol. 2008;3:221-47
pubmed: 18233952
Front Oncol. 2020 Feb 07;10:109
pubmed: 32117758
J Immunol. 2003 Feb 1;170(3):1283-90
pubmed: 12538687
Sci Immunol. 2016 Aug;1(2):
pubmed: 28417112
Nat Commun. 2018 Jan 24;9(1):355
pubmed: 29367702
Am J Clin Pathol. 2013 Jun;139(6):746-53
pubmed: 23690116
Front Immunol. 2017 Dec 11;8:1781
pubmed: 29321780
Br Med Bull. 2018 Dec 1;128(1):5-14
pubmed: 30137312
Genome Biol. 2002 Jun 18;3(7):RESEARCH0034
pubmed: 12184808
Eur J Immunol. 2011 Mar;41(3):634-44
pubmed: 21308682
Int J Surg Pathol. 2008 Oct;16(4):365-74
pubmed: 18977761
Semin Immunol. 2018 Feb;35:19-28
pubmed: 29254756
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Nucleic Acids Res. 2002 Jan 1;30(1):207-10
pubmed: 11752295
PLoS One. 2015 May 20;10(5):e0127028
pubmed: 25992611
J Clin Pathol. 2008 Feb;61(2):197-203
pubmed: 18223096
Cancer Immunol Immunother. 2020 Mar;69(3):435-448
pubmed: 31925475
Nucleic Acids Res. 2016 Jul 8;44(W1):W3-W10
pubmed: 27137889
Int J Cancer. 2016 Apr 15;138(8):1982-93
pubmed: 26619320
Int J Cancer. 2009 Aug 15;125(4):887-93
pubmed: 19431148
Oncotarget. 2017 Jan 10;8(2):3649-3665
pubmed: 27690299
Autoimmunity. 2017 May;50(3):170-181
pubmed: 28276713
J Leukoc Biol. 2014 Nov;96(5):685-93
pubmed: 24929004
J Immunol. 2005 May 15;174(10):6477-89
pubmed: 15879151
Front Immunol. 2017 Feb 06;8:86
pubmed: 28220123
Clin Immunol. 2012 Apr;143(1):83-7
pubmed: 22341087
Br J Cancer. 2015 Oct 20;113(8):1234-43
pubmed: 26448179
Gastric Cancer. 2015 Apr;18(2):306-13
pubmed: 24792410
Oncoimmunology. 2018 Jul 30;7(10):e1494113
pubmed: 30288362
Front Immunol. 2019 Sep 20;10:2155
pubmed: 31616408
Front Immunol. 2019 Aug 14;10:1912
pubmed: 31474989
Cancer Immunol Res. 2017 Jan;5(1):3-8
pubmed: 28052991
Mol Clin Oncol. 2017 Oct;7(4):515-520
pubmed: 28855985
Semin Cancer Biol. 2018 Oct;52(Pt 2):107-116
pubmed: 29935312
Blood. 2017 Mar 9;129(10):1343-1356
pubmed: 28053192
Clin Cancer Res. 2011 Nov 15;17(22):6992-7002
pubmed: 21948231
Cell Rep. 2015 Feb 3;10(4):562-73
pubmed: 25620698
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
BMC Cancer. 2010 Nov 23;10:639
pubmed: 21092276
Cancer Cell. 2004 Oct;6(4):409-21
pubmed: 15488763
Cancer Cell. 2009 Sep 8;16(3):183-94
pubmed: 19732719
Trends Cancer. 2017 Feb;3(2):149-160
pubmed: 28718445
Blood. 2016 May 5;127(18):2173-81
pubmed: 27002116
Cytometry A. 2017 Jan;91(1):34-38
pubmed: 27362704
Cancer Res. 2009 Feb 15;69(4):1553-60
pubmed: 19201693
Nat Commun. 2016 Jul 06;7:12150
pubmed: 27381735
Blood. 2013 Aug 15;122(7):1105-13
pubmed: 23757729
J Clin Invest. 2012 Jan;122(1):327-36
pubmed: 22156198
J Pediatr. 1981 Jan;98(1):101-5
pubmed: 7192731
BMC Cancer. 2012 Jul 23;12:306
pubmed: 22824040
J Clin Invest. 2007 May;117(5):1137-46
pubmed: 17476343
Eur J Immunol. 1988 Nov;18(11):1819-26
pubmed: 2849552
Cell Mol Life Sci. 2013 Oct;70(20):3813-27
pubmed: 23423530
Nat Commun. 2017 Apr 06;8:14979
pubmed: 28382931
Clin Med Res. 2009 Jun;7(1-2):4-13
pubmed: 19574486
J Immunol Res. 2015;2015:235170
pubmed: 26609537