Emphysema reprograms neutrophils toward a tumor-promoting phenotype in lung cancer.
- 1Institute of Pulmonary Medicine, Hadassah Medical Center, Jerusalem, Israel.
- 2Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Abstract
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. 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. 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. 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.
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BibTeX
@article{qaisi2026emphysema,
title = {{Emphysema reprograms neutrophils toward a tumor-promoting phenotype in lung cancer.}},
author = {Mohamad Qaisi and Merav E Shaul and Nuha Alsharif and Naomi Kaisar-Iluz and Sojod Mahroum and Osnath Bouhanna and Yael Volman and Zvi G Fridlender},
journal = {Translational lung cancer research},
year = {2026},
month = sep,
doi = {10.21037/tlcr-2026-0665},
url = {https://europepmc.org/article/MED/42999416},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Emphysema reprograms neutrophils toward a tumor-promoting phenotype in lung cancer.
AU - Mohamad Qaisi
AU - Merav E Shaul
AU - Nuha Alsharif
AU - Naomi Kaisar-Iluz
AU - Sojod Mahroum
AU - Osnath Bouhanna
AU - Yael Volman
AU - Zvi G Fridlender
PY - 2026
DA - 2026/09/28
JO - Translational lung cancer research
DO - 10.21037/tlcr-2026-0665
UR - https://europepmc.org/article/MED/42999416
AB - 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. 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. 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. 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.
SN - 2218-6751
SN - 2226-4477
ER -