Chronic Obstructive Pulmonary Disease (COPD) increases propagation of Lung cancer by reducing the cytotoxicity of neutrophils to tumor cells

COPD is a significant risk factor for lung cancer. It’s characteristic changes in lung inflammation and morphology increases the risk of lung cancer by 2-3 times. Neutrophils can contribute to tumorigenesis, but also have anti-tumor properties, and could play a crucial role in this process. We aimed to investigate how changes in neutrophils occurring in COPD, relate to the increased lung tumor growth. We established a COPD-murine model and as described, COPD caused significant increase in the extent of lung cancer. Surprisingly, depletion of neutrophils induced more severe lung cancer in mice with COPD, although with no change in the number of nodules. We next studied how COPD affects neutrophils in lung cancer. Neutrophils from lungs of mice with COPD and lung cancer had reduced ROS production, a major mechanism of direct cytotoxicity of tumor cells by neutrophils, and incresed Neutrophils Extracellular traps (NETs) release by NETosis. Neutrophils from human COPD patients had a reduction in ROS production compared to healthy volunteers. Although neutrophils from lung cancer patients had increased ROS production, this was abolished in lung cancer patients with a background of COPD. The direct ability of human neutrophils to kill tumor cells was significantly reduced in patients with lung cancer that had a background of COPD. 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. We suggest a new hypothesis explaining the link between COPD and the increased risk of lung cancer in these patients.