Protein Signature Differentiating Neutrophils and Myeloid-Derived Suppressor Cells Determined Using a Human Isogenic Cell Line Model and Protein Profiling.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

Myeloid-Derived Suppressor Cells*/metabolism ; Myeloid-Derived Suppressor Cells*/cytology ; Neutrophils*/metabolism ; Neutrophils*/cytology ; Cell Differentiation* ; Proteomics*/methods; Humans ; HL-60 Cells ; Cell Line

Myeloid-derived suppressor cells (MDSCs) play an essential role in suppressing the antitumor activity of T lymphocytes in solid tumors, thus representing an attractive therapeutic target to enhance the efficacy of immunotherapy. However, the differences in protein expression between MDSCs and their physiological counterparts, particularly polymorphonuclear neutrophils (PMNs), remain inadequately characterized, making the specific identification and targeting of MDSCs difficult. PMNs and PMN-MDSCs share markers such as CD11b+CD14-CD15+/CD66b+, and some MDSC-enriched markers are emerging, such as LOX-1 and CD84. More proteomics studies are needed to identify the signature and markers for MDSCs. Recently, we reported the induced differentiation of isogenic PMNs or MDSCs (referred to as iPMNs and iMDSCs, respectively) from the human promyelocytic cell line HL60. Here, we profiled the global proteomics and membrane proteomics of these cells with quantitative mass spectrometry, which identified a 41-protein signature ("cluster 6") that was upregulated in iMDSCs compared with HL60 and iPMN. We further integrated our cell line-based proteomics data with a published proteomics dataset of normal human primary monocytes and monocyte-derived MDSCs induced by cancer-associated fibroblasts. The analysis identified a 38-protein signature that exhibits an upregulated expression pattern in MDSCs compared with normal monocytes or PMNs. These signatures may provide a hypothesis-generating platform to identify protein biomarkers that phenotypically distinguish MDSCs from their healthy counterparts, as well as potential therapeutic targets that impair MDSCs without harming normal myeloid cells.

J Immunother Cancer. 2021 Feb;9(2):. (PMID: 33593829)
PLoS One. 2015 May 20;10(5):e0127028. (PMID: 25992611)
Int Immunopharmacol. 2002 Nov;2(12):1647-56. (PMID: 12469939)
Cancers (Basel). 2019 Oct 24;11(11):. (PMID: 31652904)
Oncoimmunology. 2024 Jan 5;13(1):2300882. (PMID: 38192443)
Cancer Immunol Immunother. 2019 Apr;68(4):673-685. (PMID: 30569204)
Br J Cancer Suppl. 1988 Dec;9:41-5. (PMID: 3076064)
Science. 2015 Apr 3;348(6230):56-61. (PMID: 25838373)
Autoimmun Rev. 2009 Sep;9(1):62-6. (PMID: 19293004)
Cells. 2023 Mar 02;12(5):. (PMID: 36899926)
Front Cell Dev Biol. 2021 Sep 28;9:732786. (PMID: 34650978)
Nucleic Acids Res. 2022 Jul 5;50(W1):W216-W221. (PMID: 35325185)
Front Immunol. 2023 Jul 03;14:1199273. (PMID: 37465670)
Arterioscler Thromb Vasc Biol. 2011 Dec;31(12):3011-9. (PMID: 21940941)
Blood. 1980 Sep;56(3):344-50. (PMID: 6996765)
BMC Bioinformatics. 2013 Apr 15;14:128. (PMID: 23586463)
Front Immunol. 2022 Dec 09;13:1021612. (PMID: 36569895)
J Immunol. 2008 Oct 1;181(7):4666-75. (PMID: 18802069)
Nat Protoc. 2009;4(1):44-57. (PMID: 19131956)
Front Immunol. 2023 Jan 17;13:1080501. (PMID: 36733385)
Immunol Lett. 1996 Apr;50(1-2):51-7. (PMID: 8793559)
Cell Metab. 2023 Oct 3;35(10):1688-1703.e10. (PMID: 37793345)
Signal Transduct Target Ther. 2021 Oct 7;6(1):362. (PMID: 34620838)
Int Rev Cell Mol Biol. 2023;375:1-31. (PMID: 36967150)
Proc Natl Acad Sci U S A. 2019 Aug 20;116(34):16971-16980. (PMID: 31375632)
Clin Exp Immunol. 2016 Dec;186(3):373-386. (PMID: 27569996)
Nucleic Acids Res. 2015 Apr 20;43(7):e47. (PMID: 25605792)
Nat Rev Immunol. 2021 Aug;21(8):485-498. (PMID: 33526920)
Int J Mol Sci. 2021 Mar 05;22(5):. (PMID: 33807717)
Transl Oncol. 2022 Mar;17:101346. (PMID: 35074719)
Cell Death Discov. 2021 Sep 4;7(1):232. (PMID: 34482371)
Oncoimmunology. 2019 Nov 3;9(1):1683347. (PMID: 32002295)
Am J Cancer Res. 2017 Nov 01;7(11):2103-2120. (PMID: 29218236)
Curr Protoc Immunol. 2019 Sep;126(1):e87. (PMID: 31483107)
Cancer Res. 2012 Feb 15;72(4):928-38. (PMID: 22237629)
Nature. 2017 Mar 30;543(7647):728-732. (PMID: 28321130)
Front Cell Dev Biol. 2021 Oct 01;9:630262. (PMID: 34660566)
Proteome Sci. 2007 Aug 10;5:12. (PMID: 17692124)
Cancer Biol Med. 2020 Feb 15;17(1):32-43. (PMID: 32296575)
Int J Mol Sci. 2020 Oct 18;21(20):. (PMID: 33081041)
Front Pharmacol. 2022 Apr 25;13:873792. (PMID: 35548341)
Front Immunol. 2017 Dec 15;8:1840. (PMID: 29326716)
Oncoimmunology. 2017 May 26;6(9):e1333213. (PMID: 28932635)
J Leukoc Biol. 2016 Sep;100(3):481-9. (PMID: 27354413)
Br J Cancer. 2019 Jan;120(1):16-25. (PMID: 30413826)
Proteome Sci. 2009 Aug 31;7:32. (PMID: 19719850)
Mol Cancer Res. 2024 Mar 1;22(3):308-321. (PMID: 38015751)
Cancer Res. 2016 Jun 1;76(11):3156-65. (PMID: 27197152)
Mutagenesis. 2002 Sep;17(5):419-24. (PMID: 12202630)
Sci Immunol. 2020 Aug 21;5(50):. (PMID: 32826342)
Nucleic Acids Res. 2022 Jan 7;50(D1):D543-D552. (PMID: 34723319)
Sci Immunol. 2016 Aug;1(2):. (PMID: 28417112)
Mol Cell Proteomics. 2013 Aug;12(8):2370-80. (PMID: 23669031)
Cell Death Dis. 2017 May 11;8(5):e2779. (PMID: 28492541)
J Cancer. 2023 Mar 5;14(4):646-656. (PMID: 37057282)
Oncoimmunology. 2013 May 1;2(5):e24064. (PMID: 23762794)
Cell Rep. 2021 Nov 2;37(5):109955. (PMID: 34731634)

n/a Boler Family Foundation; n/a Berthiaume Institute for Precision Health; R01CA248033, R01CA280097 United States NH NIH HHS; W81XWH2010312, W81XWH2010332, HT94252310010 and HT94252310613 Congressionally Directed Medical Research Programs

Keywords: immunotherapy; mass spectrometry; myeloid-derived suppressor cell; protein signature; proteomics

Date Created: 20240524 Date Completed: 20240524 Latest Revision: 20240526

20240526

PMC11119164

10.3390/cells13100795

38786019