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?

Abstract

Rationale: Chronic Obstructive Pulmonary Disease (COPD) is characterized by an excessive activation of the adaptive immune system and uncontrolled expansion of the B-cell pool. A PRoliferation-Inducing Ligand (APRIL) is a key promoter of B cell expansion. APRIL has been strongly linked to non small cell lung cancer (NSCLC) development, but little is known about its involvement in COPD.

Methods: Using immunostaining, APRIL expression was assessed in lung sections from 4 subjects with COPD, 4 subjects with NSCLC, 4 subjects diagnosed with both COPD and NSCLC, 4 smokers (SC) and non-smokers (NSC) without COPD or NSCLC. The number of APRIL-positive B cells, alveolar macrophages (AMs), polymorphonuclear neutrophils (PMNs) in the lung, and alveolar epithelial cells (AECs) was quantified.

Result: The number of APRIL-exprressing B cells, AMs, PMNs, and AECs was significantly higher in patients having both COPD and NSCLC than in patients with either COPD or NSCLC alone, SC, or NSC. The number of APRIL-expressing AMs and AECs was higher patients with NSCLC alone than in patients with COPD alone. The number of APRIL-expressing AECs was significantly higher in COPD patients than in SC and NSC. No difference in APRIL expression was found between SC and NSC.

Conclusion: APRIL was overexpressed in B cells, AMs, and AECs from the lungs of patients with both COPD and NSCLC than in patients with COPD or NSCLC alone or controls. 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.