Impact of the modulation of PD-1/ligands axis on the pulmonary response to cigarette smoke 3021

Abstract Description PD-1 and its ligands regulate lymphocyte activation and represent an important therapeutic avenue for the treatment of many cancers. However, the effects of modulating these regulatory axes in the context of smoking remain poorly studied. Some evidence suggests that there would be an alteration of the levels of PD-1 and its ligands in the context of COPD. Objective: To evaluate the effects of the administration of an antibody against PD-1 in the context of smoking on pulmonary structure and immunity. Mice were exposed to cigarette smoke (CS) for 16 weeks, followed by 4 weeks of smoking cessation. Some mice received anti-PD-1 during exposure, while others received it only during cessation. Histological analyses quantified tertiary lymphoid structure (TLS) and alveolar area (AA). Administration of anti-PD-1 in mice exposed to CS resulted in an increase of TLS formation in the lung. AA increases in the context of smoking, which is characteristic of emphysema. Administration of anti-PD-1 did not amplify this trend. However, the same treatment administered during smoking cessation appears to have reduced the increase in AA induced by CS despite the increase of TLS in the lung. Inhibition of the PD-1/ligand axis in the context of active smoking or cessation increases the formation of TLS in the lung. However, treatment during smoking cessation seems to limit the development of pulmonary emphysema. The study of immune checkpoints in pulmonary emphysema is therefore interesting. Funding Sources Supported by AIRS Network and Canadian Institutes of Health Research (CIHR) Topic Categories Immune Mechanisms of Human Disease (HUM)