AUTHOR=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 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.703846

DOI=10.3389/fimmu.2021.703846

ISSN=1664-3224

ABSTRACT=Neutrophils have been described as a phenotypically heterogenic cell type that possess both pro- and antitumor 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 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 biomarker. LDNs were highly enriched in NSCLC patients (median=19.8%, range 0.3-76.1%; n=25) 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. 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 tools.