Emphysema reprograms neutrophils toward a tumor-promoting phenotype in lung cancer
Year: 2026
Type: article
Abstract: Background: Chronic obstructive pulmonary disease (COPD), particularly emphysema, is associated with chronic lung inflammation, structural remodeling, and an increased risk of lung cancer. Although neutrophils are abundant in COPD and lung cancer, how neutrophils influence tumor development in emphysematous lungs remains unclear. We hypothesized that emphysema alters neutrophil anti-tumor functions, thereby promoting lung cancer progression. Methods: Using a mouse model of emphysema followed by lung cancer cell inoculation, we assessed the effect of neutrophil depletion on tumor growth. We then characterized neutrophil abundance, phenotype, reactive oxygen species (ROS) production, and tumor-cell cytotoxicity in blood and lungs from mice with lung cancer, with or without emphysema. Finally, we compared neutrophil functions in lung cancer patients with and without COPD. Results: In mice with emphysema and lung cancer, neutrophil depletion further increased tumor burden, indicating that neutrophils retain anti-tumor activity in this setting. While neutrophil numbers were not significantly altered by emphysema, their functional profile was changed. Lung ROS production increased in mice with lung cancer alone but was reduced in mice with lung cancer on a background of emphysema. Consistently, neutrophils from lung cancer patients with COPD showed reduced ROS production and lower cytotoxicity toward tumor cells compared with neutrophils from lung cancer patients without COPD. Conclusions: These findings suggest that emphysema impairs neutrophil anti-tumor function, reducing their cytotoxic capacity and thereby facilitating lung cancer progression. This provides a potential mechanistic link between COPD and lung cancer and highlights neutrophils as functionally important anti-tumor immune cells in the COPD-associated lung microenvironment.
Institutions: Hebrew University of Jerusalem, Hadassah Medical Center
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223958561