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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.
Karampitsakos, Theodoros; Galaris, Apostolos; Chrysikos, Serafeim; Papaioannou, Ourania; Vamvakaris, Ioannis; Barbayianni, Ilianna; Kanellopoulou, Paraskevi; Grammenoudi, Sofia; Anagnostopoulos, Nektarios; Stratakos, Grigoris; Katsaras, Matthaios; Sampsonas, Fotios; Dimakou, Katerina; Manali, Effrosyni D; Papiris, Spyridon; Tourki, Bochra; Juan-Guardela, Brenda M; Bakakos, Petros; Bouros, Demosthenes; Herazo-Maya, Jose D; Aidinis, Vassilis; Tzouvelekis, Argyris.
Afiliación
  • Karampitsakos T; Department of Respiratory Medicine, University Hospital of Patras, Rio, Greece.
  • Galaris A; Ubben Center and Laboratory for Pulmonary Fibrosis Research, Morsani College of Medicine, University of South Florida, 33620, Tampa, FL, USA.
  • Chrysikos S; Institute of Bio- Innovation, Biomedical Sciences Research Center Alexander Fleming, Athens, Greece.
  • Papaioannou O; 5th Department of Pneumonology, Hospital for Thoracic Diseases, "SOTIRIA", Athens, Greece.
  • Vamvakaris I; Department of Respiratory Medicine, University Hospital of Patras, Rio, Greece.
  • Barbayianni I; Department of Pathology, Hospital for Thoracic Diseases, "SOTIRIA", Athens, Greece.
  • Kanellopoulou P; Institute of Bio- Innovation, Biomedical Sciences Research Center Alexander Fleming, Athens, Greece.
  • Grammenoudi S; Institute of Bio- Innovation, Biomedical Sciences Research Center Alexander Fleming, Athens, Greece.
  • Anagnostopoulos N; Institute of Bio- Innovation, Biomedical Sciences Research Center Alexander Fleming, Athens, Greece.
  • Stratakos G; First Academic Department of Pneumonology, "SOTIRIA", Medical School, Hospital for Thoracic Diseases, National and Kapodistrian University of Athens, Athens, Greece.
  • Katsaras M; First Academic Department of Pneumonology, "SOTIRIA", Medical School, Hospital for Thoracic Diseases, National and Kapodistrian University of Athens, Athens, Greece.
  • Sampsonas F; Department of Respiratory Medicine, University Hospital of Patras, Rio, Greece.
  • Dimakou K; Department of Respiratory Medicine, University Hospital of Patras, Rio, Greece.
  • Manali ED; 5th Department of Pneumonology, Hospital for Thoracic Diseases, "SOTIRIA", Athens, Greece.
  • Papiris S; 2nd Pulmonary Medicine Department, Athens Medical School, "ATTIKON" University Hospital, National and Kapodistrian University of Athens, Athens, Greece.
  • Tourki B; 2nd Pulmonary Medicine Department, Athens Medical School, "ATTIKON" University Hospital, National and Kapodistrian University of Athens, Athens, Greece.
  • Juan-Guardela BM; Ubben Center and Laboratory for Pulmonary Fibrosis Research, Morsani College of Medicine, University of South Florida, 33620, Tampa, FL, USA.
  • Bakakos P; Ubben Center and Laboratory for Pulmonary Fibrosis Research, Morsani College of Medicine, University of South Florida, 33620, Tampa, FL, USA.
  • Bouros D; First Academic Department of Pneumonology, "SOTIRIA", Medical School, Hospital for Thoracic Diseases, National and Kapodistrian University of Athens, Athens, Greece.
  • Herazo-Maya JD; First Academic Department of Pneumonology, "SOTIRIA", Medical School, Hospital for Thoracic Diseases, National and Kapodistrian University of Athens, Athens, Greece.
  • Aidinis V; Ubben Center and Laboratory for Pulmonary Fibrosis Research, Morsani College of Medicine, University of South Florida, 33620, Tampa, FL, USA.
  • Tzouvelekis A; Institute of Bio- Innovation, Biomedical Sciences Research Center Alexander Fleming, Athens, Greece.
Respir Res ; 24(1): 279, 2023 Nov 14.
Article en En | MEDLINE | ID: mdl-37964265
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 immune-mediated pathways regulating fibrogenesis and carcinogenesis. PD-1 expression in mediastinal lymph nodes is in line with lung tissue expression. Lower doses of pembrolizumab might exert antifibrotic effects. Clinical trials aiming to endotype patients based on mediastinal lymph node profiling and accordingly implement targeted therapies such as PD-1 inhibitors are greatly anticipated.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fibrosis Pulmonar Idiopática / Neoplasias Pulmonares Límite: Animals / Humans Idioma: En Revista: Respir Res Año: 2023 Tipo del documento: Article País de afiliación: Grecia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fibrosis Pulmonar Idiopática / Neoplasias Pulmonares Límite: Animals / Humans Idioma: En Revista: Respir Res Año: 2023 Tipo del documento: Article País de afiliación: Grecia Pais de publicación: Reino Unido