Increased expression of A Proliferation-Inducing Ligand (APRIL) in lung leukocytes and alveolar epithelial cells in COPD patients with non small cell lung cancer: a possible link between COPD and lung cancer?

Caroline A. Owen; Francesca Polverino; Maria Laucho-Contreras; Joselyn Rojas Quintero; Miguel Divo; Victor Pinto-Plata; Lynette Sholl; Juan P. de-Torres; Bartolome R. Celli

doi:10.4081/mrm.2016.274

Increased expression of A Proliferation-Inducing Ligand (APRIL) in lung leukocytes and alveolar epithelial cells in COPD patients with non small cell lung cancer: a possible link between COPD and lung cancer?

Authors

Caroline A. Owen Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital and Harvard Medical School, Harvard Institutes of Medicine Building, Boston, MA; Lovelace Respiratory Research Institute, Albuquerque, NM
Francesca Polverino Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital and Harvard Medical School, Harvard Institutes of Medicine Building, Boston, MA; Lovelace Respiratory Research Institute, Albuquerque, NM; University of Parma, Parma
Maria Laucho-Contreras Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital and Harvard Medical School, Harvard Institutes of Medicine Building, Boston, MA
Joselyn Rojas Quintero Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital and Harvard Medical School, Harvard Institutes of Medicine Building, Boston, MA
Miguel Divo Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital and Harvard Medical School, Harvard Institutes of Medicine Building, Boston, MA; Lovelace Respiratory Research Institute, Albuquerque, NM
Victor Pinto-Plata Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital and Harvard Medical School, Harvard Institutes of Medicine Building, Boston, MA; Lovelace Respiratory Research Institute, Albuquerque, NM
Lynette Sholl Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
Juan P. de-Torres Clinica Universidad de Navarra, Pamplona
Bartolome R. Celli Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital and Harvard Medical School, Harvard Institutes of Medicine Building, Boston, MA; Lovelace Respiratory Research Institute, Albuquerque, NM

DOI: https://doi.org/10.4081/mrm.2016.274

Keywords:

Adaptive immunity, APRIL, Autoimmunity, COPD, Innate immunity, Non small cell lung cancer

Abstract

Background: Chronic Obstructive Pulmonary Disease (COPD) is characterized by an excessive activation of the adaptive immune system and, in particular, uncontrolled expansion of the B-cell pool. One of the key promoters of B cell expansion is A PRoliferation-Inducing Ligand (APRIL). APRIL has been strongly linked to non small cell lung cancer (NSCLC) onset and progression previously. However, little is known about the expression of APRIL in the lungs of COPD patients.

Methods: Using immuno-fluorescence staining, the expression of APRIL was assessed in sections of lungs from 4 subjects with primary diagnosis of COPD (FEV1 33 ± 20 % predicted), 4 subjects with primary diagnosis of NSCLC, 4 subjects diagnosed with both COPD and NSCLC, smokers without COPD or NSCLC and 3 healthy never-smokers. The percentage of B cells, alveolar macrophages (AMs) and polymorphonuclear neutrophils (PMNs) in the lung and alveolar epithelial cells (AECs) that stained positively for APRIL was quantified using epi-fluorescence microscopy and image analysis software.

Results: The percentage of APRIL-expressing B cells, AMs, PMNs and alveolar epithelial cells (AECs) was higher in patients having both COPD and NSCLC than in patients with either COPD or NSCLC alone, SC or NSC (p < 0.03 for all comparisons). The percentage of APRIL-expressing AMs and AECs (but not in B cells) was higher in patients with NSCLC alone than in patients with COPD alone. The percentage of APRIL-expressing AECs (but not B cells or AMs) was higher in COPD patients than in SC and NSC (p < 0.05 for all comparisons). The percentage of APRIL-expressing B cells, AMs and AECs cells was similar in NSC and SC.

Conclusion: The percentage of APRIL-expressing B cells, AMs and AECs is higher in the lungs of patients with both COPD and NSCLC than in patients with COPD or NSCLC alone or control subjects. These findings suggest that APRIL may contribute to the pathogenesis of both COPD and NSCLC, and possibly to the development of NSCLC in patients with established COPD.