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
© 2023. The Author(s)..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
|---|---|
| Enthalten in: |
Respiratory research - 24(2023), 1 vom: 14. Nov., Seite 279 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Karampitsakos, Theodoros [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
11056-06-7 |
|---|
| Anmerkungen: |
Date Completed 16.11.2023 Date Revised 17.11.2023 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1186/s12931-023-02551-x |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM364558768 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM364558768 | ||
| 003 | DE-627 | ||
| 005 | 20231226095704.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s12931-023-02551-x |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1215.xml |
| 035 | |a (DE-627)NLM364558768 | ||
| 035 | |a (NLM)37964265 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Karampitsakos, Theodoros |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a 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 |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 16.11.2023 | ||
| 500 | |a Date Revised 17.11.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Idiopathic pulmonary fibrosis | |
| 650 | 4 | |a Lung cancer | |
| 650 | 4 | |a Mediastinal lymph nodes | |
| 650 | 4 | |a PD-1/PD-L1 axis | |
| 650 | 4 | |a Pembrolizumab | |
| 650 | 7 | |a Programmed Cell Death 1 Receptor |2 NLM | |
| 650 | 7 | |a B7-H1 Antigen |2 NLM | |
| 650 | 7 | |a Bleomycin |2 NLM | |
| 650 | 7 | |a 11056-06-7 |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 700 | 1 | |a Galaris, Apostolos |e verfasserin |4 aut | |
| 700 | 1 | |a Chrysikos, Serafeim |e verfasserin |4 aut | |
| 700 | 1 | |a Papaioannou, Ourania |e verfasserin |4 aut | |
| 700 | 1 | |a Vamvakaris, Ioannis |e verfasserin |4 aut | |
| 700 | 1 | |a Barbayianni, Ilianna |e verfasserin |4 aut | |
| 700 | 1 | |a Kanellopoulou, Paraskevi |e verfasserin |4 aut | |
| 700 | 1 | |a Grammenoudi, Sofia |e verfasserin |4 aut | |
| 700 | 1 | |a Anagnostopoulos, Nektarios |e verfasserin |4 aut | |
| 700 | 1 | |a Stratakos, Grigoris |e verfasserin |4 aut | |
| 700 | 1 | |a Katsaras, Matthaios |e verfasserin |4 aut | |
| 700 | 1 | |a Sampsonas, Fotios |e verfasserin |4 aut | |
| 700 | 1 | |a Dimakou, Katerina |e verfasserin |4 aut | |
| 700 | 1 | |a Manali, Effrosyni D |e verfasserin |4 aut | |
| 700 | 1 | |a Papiris, Spyridon |e verfasserin |4 aut | |
| 700 | 1 | |a Tourki, Bochra |e verfasserin |4 aut | |
| 700 | 1 | |a Juan-Guardela, Brenda M |e verfasserin |4 aut | |
| 700 | 1 | |a Bakakos, Petros |e verfasserin |4 aut | |
| 700 | 1 | |a Bouros, Demosthenes |e verfasserin |4 aut | |
| 700 | 1 | |a Herazo-Maya, Jose D |e verfasserin |4 aut | |
| 700 | 1 | |a Aidinis, Vassilis |e verfasserin |4 aut | |
| 700 | 1 | |a Tzouvelekis, Argyris |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Respiratory research |d 2000 |g 24(2023), 1 vom: 14. Nov., Seite 279 |w (DE-627)NLM115627553 |x 1465-993X |7 nnns |
| 773 | 1 | 8 | |g volume:24 |g year:2023 |g number:1 |g day:14 |g month:11 |g pages:279 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1186/s12931-023-02551-x |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 24 |j 2023 |e 1 |b 14 |c 11 |h 279 | ||