Similar programmed death ligand 1 (PD-L1) expression profile in patients with mild COPD and lung cancer

作者：Francesca Polverino, Davida Mirra, Chen Xi Yang, Renata Esposito, Giuseppe Spaziano, Joselyn Rojas, Manuela Sgambato, Elena Piegari, A Cozzolino, Erika Cione, Luca Gallelli, A. Capuozzo, Carlo Santoriello, Liberato Berrino, Juan Pablo de-Torres, Tillie‐Louise Hackett, Mario Polverino, Bruno D’Agostino · 发表于：Scientific Reports · 年份：2022 · DOI：10.1038/s41598-022-26650-9 · 被引用次数：36 · 研究领域：Cancer Immunotherapy and Biomarkers、Immune cells in cancer、Ferroptosis and cancer prognosis

Abstract Programmed Death Ligand 1 (PD-L1) is crucial in regulating the immunological tolerance in non-small cell lung cancer (NSCLC). Alveolar macrophage (AM)-derived PD-L1 binds to its receptor, PD-1, on surveilling lymphocytes, leading to lymphocyte exhaustion. Increased PD-L1 expression is associated with cigarette smoke (CS)-exposure. However, the PD-L1 role in CS-associated lung diseases associated with NSCLC, such as chronic obstructive pulmonary disease (COPD), is still unclear. In two different cohorts of ever smokers with COPD or NSCLC, and ever and never smoker controls, we evaluated PD-L1 expression: (1) via cutting-edge digital spatial proteomic and transcriptomic profiling (Geomx) of formalin-fixed paraffin-embedded (FFPE) lung tissue sections (n = 19); and (2) via triple immunofluorescence staining of bronchoalveolar lavage (BAL) AMs (n = 83). PD-L1 mRNA expression was also quantified in BAL AMs exposed to CS extract. PD-L1 expression was increased in the bronchiolar wall, parenchyma, and vascular wall from mild-moderate (GOLD 1–2) COPD patients compared to severe-very severe (GOLD 3–4) COPD patients and controls. Within all the COPD patients, PD-L1 protein expression was associated with upregulation of genes involved in tumor progression and downregulation of oncosuppressive genes, and strongly directly correlated with the FEV 1 % predicted, indicating higher PD-L1 expression in the milder vs. more severe COPD stages. In bronchioles, PD-L1 levels were strongly...