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
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2021
Historique:
received: 30 04 2021
accepted: 15 07 2021
entrez: 6 9 2021
pubmed: 7 9 2021
medline: 18 12 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 34484199
doi: 10.3389/fimmu.2021.703846
pmc: PMC8414579
doi:

Substances chimiques

Antigens, CD 0
Biomarkers, Tumor 0
Neoplasm Proteins 0

Types de publication

Clinical Trial Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

703846

Subventions

Organisme : Austrian Science Fund FWF
ID : DOC 31
Pays : Austria
Organisme : NCI NIH HHS
ID : P50 CA228944
Pays : United States

Informations de copyright

Copyright © 2021 Valadez-Cosmes, Maitz, Kindler, Raftopoulou, Kienzl, Santiso, Mihalic, Brcic, Lindenmann, Fediuk, Pichler, Schicho, Houghton, Heinemann and Kargl.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Paulina Valadez-Cosmes (P)

Otto Loewi Research Center, Division of Pharmacology, Medical University of Graz, Graz, Austria.

Kathrin Maitz (K)

Otto Loewi Research Center, Division of Pharmacology, Medical University of Graz, Graz, Austria.

Oliver Kindler (O)

Otto Loewi Research Center, Division of Pharmacology, Medical University of Graz, Graz, Austria.

Sofia Raftopoulou (S)

Otto Loewi Research Center, Division of Pharmacology, Medical University of Graz, Graz, Austria.

Melanie Kienzl (M)

Otto Loewi Research Center, Division of Pharmacology, Medical University of Graz, Graz, Austria.
BioTechMed, Graz, Austria.

Ana Santiso (A)

Otto Loewi Research Center, Division of Pharmacology, Medical University of Graz, Graz, Austria.

Zala Nikita Mihalic (ZN)

Otto Loewi Research Center, Division of Pharmacology, Medical University of Graz, Graz, Austria.

Luka Brcic (L)

Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria.

Jörg Lindenmann (J)

Division of Thoracic and Hyperbaric Surgery, Department of Surgery, Medical University of Graz, Graz, Austria.

Melanie Fediuk (M)

Division of Thoracic and Hyperbaric Surgery, Department of Surgery, Medical University of Graz, Graz, Austria.

Martin Pichler (M)

Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.

Rudolf Schicho (R)

Otto Loewi Research Center, Division of Pharmacology, Medical University of Graz, Graz, Austria.
BioTechMed, Graz, Austria.

A McGarry Houghton (AM)

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA, United States.

Akos Heinemann (A)

Otto Loewi Research Center, Division of Pharmacology, Medical University of Graz, Graz, Austria.
BioTechMed, Graz, Austria.

Julia Kargl (J)

Otto Loewi Research Center, Division of Pharmacology, Medical University of Graz, Graz, Austria.
BioTechMed, Graz, Austria.

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