The Multifaceted Roles of Neutrophil Death in COPD and Lung Cancer

Abstract

Chronic obstructive pulmonary disease (COPD) and lung cancer are closely linked, with individuals suffering from COPD at a significantly higher risk of developing lung cancer. The mechanisms driving this increased risk are multifaceted, involving genomic instability, immune dysregulation, and alterations in the lung environment. Neutrophils, the most abundant myeloid cells in human blood, have emerged as critical regulators of inflammation in both COPD and lung cancer. Despite their short lifespan, neutrophils contribute to disease progression through various forms of programmed cell death, including apoptosis, necroptosis, ferroptosis, pyroptosis, and NETosis, a form of neutrophil death with neutrophil extracellular traps (NETs) formation. These distinct death pathways affect inflammatory responses, tissue remodeling, and disease progression in COPD and lung cancer. This review provides an in-depth exploration of the mechanisms regulating neutrophil death, the interplay between various cell death pathways, and their influence on disease progression. Additionally, we highlight emerging therapeutic approaches aimed at targeting neutrophil death pathways, presenting promising new interventions to enhance treatment outcomes in COPD and lung cancer.

Keywords

Nuetrophil / Cell death / COPD / Lung cancer

Acknowledgments

The authors thank the reviewers and the editors for their suggestions.

Author Contributions

A.W. and D.C. wrote the manuscript. A.W. created the tables and figures. D.C. edited the manuscript. All authors have read and agreed to the published version of the manuscript.

Ethics Statement

Not applicable.

Informed Consent Statement

Not applicable.

Funding

This work was supported by the National Institutes of Health NIH (R56HL162749, D.C.), Wright Foundation Standard Pilot Grant (D.C.), American Cancer Society Pilot Grant (#IRG –22-144-60, D.C.), and the University of Southern California Start-up Fund (D.C.).

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work presented in this paper. Figures were generated with BioRender (https://app.biorender.com/illustrations).

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