Chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) are two respiratory conditions of significant global importance. COPD is characterized by chronic airway inflammation, leading to persistent and progressive airflow obstruction 1. It is often associated with cigarette smoking, and represents a significant risk factor for the development of NSCLC. Programmed Death Ligand 1 (PD-L1) is critical for establishment of immune escape facilitating the tumor initiation, development and progression.2,3 Its overexpression was observed on the cell surface of different types of cancer cells, including NSCLC (Non Small Cell Lung Cancer)4. COPD because of the chronic inflammation might create a favorable immunosuppressive microenvironment with a possible dysregulated immune tolerance (T-cell exhaustion due to the binding of immune checkpoints on T-cells) 2,3. AIM: The aim was to evaluate PD-L1 expression in patients with and without COPD and concomitant NSCLC and to investigate the relation with clinical and inflammatory features. METHODS: In this retrospective observational study conducted at the Pneumology Unit of the University Hospital of Padua, we enrolled 71 patients with a diagnosis of NSCLC, regardless of age, gender, and disease stage. They were classified into three groups: 1. Smokers (current or former) with COPD; 2. Smokers without COPD; 3.Non-smokers. In each group, the expression of PD-L1 in lung biopsies was evaluated, together with medical history, spirometric, and laboratory data. RESULTS: 35 out of 71 patients with NSCLC were smokers with mild-moderate COPD (FEV1 67±16%), 21 smokers without COPD (99±12%), and 15 non-smokers (100±17%). Tissue expression of PD-L1 was higher in COPD smokers (20 [4.5-56]%) compared to smokers without COPD (2 [0-21]%; p=0.05) and non-smokers (1 [0-21]%; p=0.05). Squamous cell carcinoma was more common among smokers with COPD compared to non-smokers (14/35 vs 1/15; p=0.02). PD-L1 expression was similar across different tumor histologies, genders, and tumor stages (advanced 28±31%, early 18±26%). No correlation was identified between PD-L1 and pack-years, differential cell count, or lung function. Overall, patients with an FEV1 <67% of predicted (25th percentile) had fewer circulating lymphocytes (19±6 vs 26±8%; p=0.01) and a higher neutrophil-to-lymphocyte ratio (4±3 vs 3±2; p=0.01) compared to those with higher FEV1 values. CONCLUSIONS: The expression of PD-L1 is significantly higher in smoking patients with NSCLC and COPD compared to those without COPD, suggesting that the alteration of the adaptive immune response present in COPD contributes to PD-L1 expression and may therefore have therapeutic implications.

Exploring PD-L1 expression on patients with NSCLC and COPD: preliminary results

FERRARA, MARTINA MARIA
2022/2023

Abstract

Chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) are two respiratory conditions of significant global importance. COPD is characterized by chronic airway inflammation, leading to persistent and progressive airflow obstruction 1. It is often associated with cigarette smoking, and represents a significant risk factor for the development of NSCLC. Programmed Death Ligand 1 (PD-L1) is critical for establishment of immune escape facilitating the tumor initiation, development and progression.2,3 Its overexpression was observed on the cell surface of different types of cancer cells, including NSCLC (Non Small Cell Lung Cancer)4. COPD because of the chronic inflammation might create a favorable immunosuppressive microenvironment with a possible dysregulated immune tolerance (T-cell exhaustion due to the binding of immune checkpoints on T-cells) 2,3. AIM: The aim was to evaluate PD-L1 expression in patients with and without COPD and concomitant NSCLC and to investigate the relation with clinical and inflammatory features. METHODS: In this retrospective observational study conducted at the Pneumology Unit of the University Hospital of Padua, we enrolled 71 patients with a diagnosis of NSCLC, regardless of age, gender, and disease stage. They were classified into three groups: 1. Smokers (current or former) with COPD; 2. Smokers without COPD; 3.Non-smokers. In each group, the expression of PD-L1 in lung biopsies was evaluated, together with medical history, spirometric, and laboratory data. RESULTS: 35 out of 71 patients with NSCLC were smokers with mild-moderate COPD (FEV1 67±16%), 21 smokers without COPD (99±12%), and 15 non-smokers (100±17%). Tissue expression of PD-L1 was higher in COPD smokers (20 [4.5-56]%) compared to smokers without COPD (2 [0-21]%; p=0.05) and non-smokers (1 [0-21]%; p=0.05). Squamous cell carcinoma was more common among smokers with COPD compared to non-smokers (14/35 vs 1/15; p=0.02). PD-L1 expression was similar across different tumor histologies, genders, and tumor stages (advanced 28±31%, early 18±26%). No correlation was identified between PD-L1 and pack-years, differential cell count, or lung function. Overall, patients with an FEV1 <67% of predicted (25th percentile) had fewer circulating lymphocytes (19±6 vs 26±8%; p=0.01) and a higher neutrophil-to-lymphocyte ratio (4±3 vs 3±2; p=0.01) compared to those with higher FEV1 values. CONCLUSIONS: The expression of PD-L1 is significantly higher in smoking patients with NSCLC and COPD compared to those without COPD, suggesting that the alteration of the adaptive immune response present in COPD contributes to PD-L1 expression and may therefore have therapeutic implications.
2022
Exploring PD-L1 expression on patients with NSCLC and COPD: preliminary results
PD-L1
NSCLC
COPD
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12608/81353