Myeloperoxidase promotes a tumorigenic microenvironment in non-small cell lung cancer
7 affiliations
- 1Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, Austria
- 2Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, Austria; BioTechMed, Graz, Austria
- 3Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria
- 4Division of Thoracic and Hyperbaric Surgery, Department of Surgery, Medical University of Graz, Graz, Austria
- 5BioTechMed, Graz, Austria; Division of Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria
- 6Clinical 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
- 7Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, Austria; BioTechMed, Graz, Austria; Corresponding author. Medical University of Graz, Neue Stiftintalstrasse 6, 8010, Graz, Austria.
Abstract
Myeloperoxidase (MPO) is a heme peroxidase that is mainly expressed and secreted by neutrophils. MPO's role in inflammatory diseases has been highlighted in recent years, but its role in tumor development remains unclear. Therefore, we investigated the role of MPO in non-small cell lung cancer (NSCLC). In silico analysis revealed a survival benefit in patients with NSCLC and low MPO expression. Furthermore, a syngeneic tumor model using MPO knockout (KO) mice revealed that mice lacking MPO had lower tumor growth than controls. The reduction in tumor size was accompanied by an increase in lymphoid populations, including natural killer cells and CD8 + T cells, suggesting a shift to a more anti-tumorigenic immune environment in MPO-KO mouse tumors. The T cell induced interferon-gamma (IFN-γ) expression was increased in MPO-KO tumors, indicating increased tumoricidal activity. CD8 depletion abolished the previously observed reduction in tumor size in MPO-KO mice, indicating that CD8 + T cells play an important role. In vitro, T cells treated with MPO showed reduced proliferation and IFN-γ expression. Furthermore, MPO associated directly with T cells. Interestingly, MPO + lymphocytes, including CD8 + T cells, were found in tumor samples from patients with NSCLC. Our findings suggest that MPO plays an immunosuppressive role in NSCLC.
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BibTeX
@article{valadezcosmes2026myeloperoxidase,
title = {{Myeloperoxidase promotes a tumorigenic microenvironment in non-small cell lung cancer}},
author = {Paulina Valadez-Cosmes and Kathrin Maitz and Anna Lagler and Oliver Kindler and Nejra Cosic Mujkanovic and Sofia Raftopoulou and Melanie Kienzl and Zala Nikita Juvan and Ana Santiso and Luka Brcic and Gregor Gorkiewicz and Jörg Lindenmann and Wolfgang Sattler and Akos Heinemann and Rudolf Schicho and Gunther Marsche and A. McGarry Houghton and Julia Kargl},
journal = {Redox Biology},
year = {2026},
month = oct,
doi = {10.1016/j.redox.2026.104399},
url = {https://doi.org/10.1016/j.redox.2026.104399},
note = {CC BY},
}
RIS
TY - JOUR
TI - Myeloperoxidase promotes a tumorigenic microenvironment in non-small cell lung cancer
AU - Paulina Valadez-Cosmes
AU - Kathrin Maitz
AU - Anna Lagler
AU - Oliver Kindler
AU - Nejra Cosic Mujkanovic
AU - Sofia Raftopoulou
AU - Melanie Kienzl
AU - Zala Nikita Juvan
AU - Ana Santiso
AU - Luka Brcic
AU - Gregor Gorkiewicz
AU - Jörg Lindenmann
AU - Wolfgang Sattler
AU - Akos Heinemann
AU - Rudolf Schicho
AU - Gunther Marsche
AU - A. McGarry Houghton
AU - Julia Kargl
PY - 2026
DA - 2026/10/30
JO - Redox Biology
DO - 10.1016/j.redox.2026.104399
UR - https://doi.org/10.1016/j.redox.2026.104399
AB - Myeloperoxidase (MPO) is a heme peroxidase that is mainly expressed and secreted by neutrophils. MPO's role in inflammatory diseases has been highlighted in recent years, but its role in tumor development remains unclear. Therefore, we investigated the role of MPO in non-small cell lung cancer (NSCLC). In silico analysis revealed a survival benefit in patients with NSCLC and low MPO expression. Furthermore, a syngeneic tumor model using MPO knockout (KO) mice revealed that mice lacking MPO had lower tumor growth than controls. The reduction in tumor size was accompanied by an increase in lymphoid populations, including natural killer cells and CD8 + T cells, suggesting a shift to a more anti-tumorigenic immune environment in MPO-KO mouse tumors. The T cell induced interferon-gamma (IFN-γ) expression was increased in MPO-KO tumors, indicating increased tumoricidal activity. CD8 depletion abolished the previously observed reduction in tumor size in MPO-KO mice, indicating that CD8 + T cells play an important role. In vitro, T cells treated with MPO showed reduced proliferation and IFN-γ expression. Furthermore, MPO associated directly with T cells. Interestingly, MPO + lymphocytes, including CD8 + T cells, were found in tumor samples from patients with NSCLC. Our findings suggest that MPO plays an immunosuppressive role in NSCLC.
SN - 2213-2317
ER -