Abstract
A high smoking-independent chronic obstructive pulmonary disease (COPD) prevalence is observed in lung cancer patients. However, the underlying connection between these two diseases still remains unclear. Cigarette smoking and ambient air pollution are common risk factors for COPD and lung cancer. In this study, we established rat COPD model through exposure to cigarette smoke (CS) or motor vehicle exhaust (MVE). The model rats developed COPD-like phenotypes, manifested as lung functions decline, lung inflammation, emphysema-like alveolar enlargement and airway remodeling. The programmed death-ligand 1 (PD-L1), a factor contributing to immune escape of tumor cells, was overexpressed in lungs from COPD model rats, though more severe COPD phenotypes did not bring with further PD-L1 overexpression in lung. The upregulations of proinflammatory cytokines and PD-L1 were also observed in cultured human bronchial epithelial cells BEAS-2B upon treatment with cigarette smoke extract (CSE) or diesel-related particulate matter 2.5 (PM2.5, SEM1650b). The inflammatory cytokines produced in BEAS-2B cells reflected the PD-L1 levels. Furthermore, ERK1/2, a kinase mediating PD-L1 upregulation in premalignant bronchial cells or NSCLC cells, and STAT1/3, which was reportedly associated with PD-L1 expression in lung tumors, were activated in COPD rats' lungs or in BEAS-2B cells treated with CSE or PM2.5. Therefore, we proposed that inflammation associated PD-L1 overexpression in airway epithelial cells could be the underlying factor facilitating lung cancer incidence in COPD.