Identification of Novel Low-Density Neutrophil Markers Through Unbiased High-Dimensional Flow Cytometry Screening in Non-Small Cell Lung Cancer Patients

Neutrophils have been described as a phenotypically heterogeneous cell type that possess both pro- and anti-tumor properties. Recently, a subset of neutrophils isolated from the peripheral blood mononuclear cell (PBMC) fraction has been described in cancer patients. These low-density neutrophils (LD...

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Published inFrontiers in immunology Vol. 12; p. 703846
Main Authors Valadez-Cosmes, Paulina, Maitz, Kathrin, Kindler, Oliver, Raftopoulou, Sofia, Kienzl, Melanie, Santiso, Ana, Mihalic, Zala Nikita, Brcic, Luka, Lindenmann, Jörg, Fediuk, Melanie, Pichler, Martin, Schicho, Rudolf, Houghton, A McGarry, Heinemann, Akos, Kargl, Julia
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 13.08.2021
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Summary:Neutrophils have been described as a phenotypically heterogeneous cell type that possess both pro- and anti-tumor properties. Recently, a subset of neutrophils isolated from the peripheral blood mononuclear cell (PBMC) fraction has been described in cancer patients. These low-density neutrophils (LDNs) show a heterogeneous maturation state and have been associated with pro-tumor properties in comparison to mature, high-density neutrophils (HDNs). However, additional studies are necessary to characterize this cell population. Here we show new surface markers that allow us to discriminate between LDNs and HDNs in non-small cell lung cancer (NSCLC) patients and assess their potential as diagnostic/prognostic tool. LDNs were highly enriched in NSCLC patients (median=20.4%, range 0.3-76.1%; n=26) but not in healthy individuals (median=0.3%, range 0.1-3.9%; n=14). Using a high-dimensional human cell surface marker screen, we identified 12 surface markers that were downregulated in LDNs when compared to HDNs, while 41 surface markers were upregulated in the LDN subset. Using flow cytometry, we confirmed overexpression of CD36, CD41, CD61 and CD226 in the LDN fraction. In summary, our data support the notion that LDNs are a unique neutrophil population and provide novel targets to clarify their role in tumor progression and their potential as diagnostic and therapeutic tool.
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This article was submitted to Molecular Innate Immunity, a section of the journal Frontiers in Immunology
Edited by: Dragana Odobasic, Monash University, Australia
Reviewed by: Anja Meissner, Lund University, Sweden; Tamás Laskay, University of Lübeck, Germany
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.703846