Role for the PD-1/PD-L1 axis in the development of COPD

Background: Smoking is the main cause for the development of the chronic obstructive pulmonary disease (COPD). Bacterial pathogens (e.g. Nontypeable Haemophilus influenzae (NTHi)) are frequently found in lungs of stable COPD patients. Antibodies that specifically block the receptor programmed death 1 (PD-1) have demonstrated efficacy as therapeutic agents for non-small cell lung cancer.

Methods: Mice were chronically exposed to CS or NTHi and treated with an antibody targeting PD-1 or an isotype antibody. Concentrations of PD-1 and PD-L1 were measured in serum collected from stabile COPD patients and during acute exacerbations (AECOPD) and in BAL fluids of stable patients.

Results: Chronic exposure of mice to CS or NTHi associated with an increased expression of PD-1 and PD-L1 in lung tissue. Anti-PD-1 treatment decreased lung damage and neutrophilic inflammation. PD-L1 concentrations correlated positively with PD-1 concentrations in serum and BAL fluids. The ratio of PD-1 to PD-L1 in BAL fluids correlated with disease severity (FEV1 predicted, GOLD III/IV).

Conclusions: The PD-1/PD-L1 axis is involved in the development of inflammation and tissue destruction in COPD. Inflammation-induced activation of the PD-1 pathway may contribute to disease progression.