Differential expression of PD-1/PD-L1 axis and CD4/CD8 ratio in mediastinal lymph nodes of patients with idiopathic pulmonary fibrosis and lung cancer

Abstract

Introduction: Mediastinal lymph node enlargement is prevalent in patients with idiopathic pulmonary fibrosis (IPF). Studies investigating whether this phenomenon reflects specific immunologic activation are lacking.

Aim: To compare the expression of PD-1/PD-L1 axis and CD4/CD8 ratio in mediastinal lymph nodes of patients with IPF and lung cancer.

Methods: Lymph node sampling was performed through endobronchial ultrasound (EBUS) bronchoscopy. The percentage of PD-1/PD-L1 positive and CD4/CD8 lymphocytes was measured.

Results: Thirty two patients (n=32) were enrolled in the study (IPF: n=13, lung cancer: n=10, concomitant IPF and lung cancer: n=9). Median PD-1% expression was significantly higher in lymphocytes of patients with IPF compared to lung cancer (2.0, 95% CI: 0.5 to 3.0, vs. 0.0, 95% CI: 0.0 to 0.8, p=0.006). Median PD-L1% expression was significantly lower in lymphocytes of patients with IPF compared to lung cancer (0.0, 95% CI: 0.0 to 0.5, vs. 1.5, 95% CI: 0.0 to 2.5, p=0.04). Median CD4/CD8 ratio was significantly higher in lymph nodes of patients with IPF compared to patients with lung cancer (1.9, 95% CI: 1.2 to 2.6, vs. 0.9, 95% CI: 0.7 to 1.3, p=0.0007). There were no significant differences in the expression of PD-1/PD-L1 axis and CD4/CD8 between patients with lung cancer and patients with concomitant IPF and lung cancer.

Conclusion: Mediastinal lymph nodes of patients with IPF exhibit differential expression profiles of lymphocyte subpopulations than patients with lung cancer indicating distinct immune-mediated pathways regulating fibrogenesis and carcinogenesis. Further mechanistic studies are eagerly awaited.