What question did this study set out to answer?

This study investigates how COPD alters neutrophil function and its impact on lung cancer progression.

May 20, 2026

B21-03 Chronic Obstructive Pulmonary Disease (COPD) Increases Propagation of Lung Cancer by Reducing the Cytotoxicity of Neutrophils to Tumor Cells

Key Points

This study investigates how COPD alters neutrophil function and its impact on lung cancer progression.
Mouse model of COPD induced by elastase and lipopolysaccharide (LPS) was used.
Neutrophil depletion effects on tumor growth were assessed in COPD mice.
Comparison was made with human lung cancer patients with and without COPD.
Neutrophil depletion in COPD mice resulted in tumor growth of 6.2 +/- 1.51 mm2 compared to 1.3 +/- 0.031 mm2 in non-depleted mice (p < 0.05).
Mice with COPD and lung cancer showed reduced reactive oxygen species (ROS) production and increased NETosis.
Human lung cancer patients without COPD had higher cytotoxicity towards tumor cells (62.2% +/- 6.55%) compared to those with COPD (38.22% +/- 7.5%, n=17, p=0.027).

Abstract

Abstract Rationale The changes in lung inflammation patterns and lung morphology (e.g., emphysema) which characterize COPD are known to increase the risk of lung cancer by 2-3 folds. Neutrophils can contribute to tumorigenesis, yet they also possess anti-tumor properties and are capable of killing tumor cells directly. In the current study we investigated how changes in neutrophils, occurring in COPD are related to the increased lung tumor dissemination and growth. We hypothesized that altered neutrophil function in COPD contributes to LC progression. Methods In a mouse model of COPD, induced by nasal instillation of elastase and lipopolysaccharide (LPS), we assessed the impact of neutrophil depletion on tumor growth. We analyzed neutrophil phenotype and function in blood and lungs of mice with LC ± COPD and compared these findings with human LC patients with and without COPD. Results Tumor growth increased after neutrophil depletion in COPD mice - 6.2 +/- 1.51 mm2 in neutrophils-depleted mice compared to 1.3 +/- 0.031 mm2 in mice without depletion (p 0.05). While neutrophil numbers were unchanged, mice with both COPD and LC showed reduced ROS production, a major mechanism of direct cytotoxicity to tumor cells, and increased NETosis. Similarly, neutrophils from human lung cancer patients without a previous diagnosis of COPD produced higher levels of ROS with a mean AUC of 3.75 X 108 +/- 0.39 X 108 compared to 2.6 X 108 +/- 0.35 X 108 in lung cancer patients with known COPD (n = 33, p = 0.049). Remarkably, lung cancer patients without COPD had also higher direct cytotoxicity towards tumor cells, 62.2% +/- 6.55% compared to 38.22% +/- 7.5% in patients with COPD (n = 17, p = 0.027). Conclusions Overall, our findings suggest that COPD reduces the capability of neutrophils to secrete ROS and kill tumor cells, thus allowing better propagation of tumor growth in the lungs. Neutrophil cytotoxicity is impaired in COPD, potentially facilitating LC development. We suggest a new hypothesis explaining the link between COPD and the increased risk of lung cancer in these patients, mediated by neutrophils modification, and highlighting neutrophils’ anti-tumor role, impaired in COPD. This abstract is funded by: Sasson and Luiza Naor Fund

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