Expression of PD-1/PD-L1 axis in mediastinal lymph nodes and lung tissue of human and experimental lung fibrosis indicates a potential therapeutic target for idiopathic pulmonary fibrosis

作者：Τheodoros Karampitsakos, Apostolos Galaris, Serafeim Chrysikos, Ουρανία Παπαϊωάννου, Ioannis Vamvakaris, Ilianna Barbayianni, Paraskevi Kanellopoulou, Sofia Grammenoudi, Nektarios Anagnostopoulos, Grigoris Stratakos, Matthaios Katsaras, Fotios Sampsonas, Katerina Dimakou, Effrosyni D. Manali, Spyridon Papiris, Bochra Tourki, Brenda Juan-Guardela, Petros Bakakos, Demosthenes Bouros, Jose D. Herazo‐Maya, Vassilis Aidinis, Argyris Tzouvelekis · 发表于：Respiratory Research · 年份：2023 · DOI：10.1186/s12931-023-02551-x · 被引用次数：30 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Cancer Immunotherapy and Biomarkers、Lung Cancer Diagnosis and Treatment

BACKGROUND: Mediastinal lymph node enlargement is prevalent in patients with idiopathic pulmonary fibrosis (IPF). Studies investigating whether this phenomenon reflects specific immunologic activation are lacking. METHODS: Programmed cell death-1 (PD-1)/ programmed cell death ligand-1 (PD-L1) expression in mediastinal lymph nodes and lung tissues was analyzed. PD-1, PD-L1 mRNA expression was measured in tracheobronchial lymph nodes of mice following bleomycin-induced injury on day 14. Finally, the effect of the PD-1 inhibitor, pembrolizumab, in bleomycin-induced pulmonary fibrosis was investigated. RESULTS: We analyzed mediastinal lymph nodes of thirty-three patients (n = 33, IPF: n = 14, lung cancer: n = 10, concomitant IPF and lung cancer: n = 9) and lung tissues of two hundred nineteen patients (n = 219, IPF: 123, controls: 96). PD-1 expression was increased, while PD-L1 expression was decreased, in mediastinal lymph nodes of patients with IPF compared to lung cancer and in IPF lungs compared to control lungs. Tracheobronchial lymph nodes isolated on day 14 from bleomycin-treated mice exhibited increased size and higher PD-1, PD-L1 mRNA levels compared to saline-treated animals. Pembrolizumab blunted bleomycin-induced lung fibrosis, as indicated by reduction in Ashcroft score and improvement in respiratory mechanics. CONCLUSIONS: Mediastinal lymph nodes of patients with IPF exhibit differential expression profiles than those of patients with lung cancer indicating distinct...