Similar Programmed Death Ligand 1 expression profile in COPD and NSCLC structural and immune cells

Abstract

<b>Introduction and background:</b> Programmed Death Ligand 1 (PD-L1) is crucial in regulating the immunological tolerance in non-small cell lung cancer (NSCLC). However, the PD-L1 expression in chronic obstructive pulmonary disease (COPD) in the context of NSCLC is still unknown. <b>Aims and objectives:</b> Analysis of PD-L1 expression in peripheral lung from patients with COPD, NSCLC, and controls. <b>Methods:</b> In two different cohorts of patients with COPD alone, NSCLC alone, COPD with NSCLC, ever and never smoker controls we evaluated PD-L1 expression via: 1) cutting-edge digital spatial proteomic (n=18); and 2) triple immunofluorescence staining of bronchoalveolar lavage alveolar macrophages (AMs, n=83). <b>Results:</b> PD-L1 expression was increased in the bronchiolar, alveolar, and vascular wall from Global initiative for chronic lung disease (GOLD) 1-2 COPD patients compared to patients with GOLD 3-4 COPD, and controls. Within all the COPD patients, bronchiolar PD-L1 protein expression was strongly directly correlated with the FEV1% pred., indicating higher PD-L1 expression in milder COPD stages, and with the number of CD68+ functionally active AMs. In BAL, both GOLD 1-2 COPD and NSCLC AMs had similar PD-L1 expression levels, much higher than all the other patients’ groups. Conclusions: Mild COPD is characterized by a strong PD-L1 expression signature in bronchioles and functionally active AMs similar to that observed in NSCLC, suggesting that in mild COPD a blunted immune environment might facilitate the development and/or progression to NSCLC. These observations represent a new resource in understanding the immune mechanisms underlying the link between COPD and lung cancer onset and progression.