Influence of Malignant Pleural Fluid from Lung Adenocarcinoma Patients on Neutrophil Response

Simple Summary This study provides novel information about the role of neutrophils in malignant pleural effusion (MPE) and hallmarks their clinical relevance. Since these cells have emerged as important regulators of cancer, we characterized their phenotype and functions in MPE microenvironment. We...

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Authors: Mulet, M, Osuna-Gomez, R, Zamora, C, Porcel, JM, Nieto, JC, Perea, L, Pajares, V, Munoz-Fernandez, AM, Calvo, N, Sorolla, MA, Vidal, S
Format: article
Status:Published version
Publication Date:2022
Country:España
Institution:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repository:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p11252
Online Access:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11252
https://ddd.uab.cat/record/284180
Access Level:Open access
Keyword:malignant pleural fluid
lung adenocarcinoma
neutrophils
NETosis
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spelling Influence of Malignant Pleural Fluid from Lung Adenocarcinoma Patients on Neutrophil ResponseMulet, MOsuna-Gomez, RZamora, CPorcel, JMNieto, JCPerea, LPajares, VMunoz-Fernandez, AMCalvo, NSorolla, MAVidal, Smalignant pleural fluidlung adenocarcinomaneutrophilsNETosisSimple Summary This study provides novel information about the role of neutrophils in malignant pleural effusion (MPE) and hallmarks their clinical relevance. Since these cells have emerged as important regulators of cancer, we characterized their phenotype and functions in MPE microenvironment. We found that neutrophil-derived products (degranulation molecules and neutrophil extracellular traps (NETs)) were increased in MPE. In addition, NETs were associated with a worse outcome in lung adenocarcinoma patients with MPE. Malignant pleural effusion (MPE) is a common severe complication of advanced lung adenocarcinoma (LAC). Neutrophils, an essential component of tumor infiltrates, contribute to tumor progression and their counts in MPE have been associated with worse outcome in LAC. This study aimed to evaluate phenotypical and functional changes of neutrophils induced by MPE to determine the influence of MPE immunomodulatory factors in neutrophil response and to find a possible association between neutrophil functions and clinical outcomes. Pleural fluid samples were collected from 47 LAC and 25 heart failure (HF) patients. We measured neutrophil degranulation products by ELISA, oxidative burst capacity and apoptosis by flow cytometry, and NETosis by fluorescence. The concentration of degranulation products was higher in MPE-LAC than in PE-HF. Functionally, neutrophils cultured with MPE-LAC had enhanced survival and neutrophil extracellular trap (NET) formation but had reduced oxidative burst capacity. In MPE, NETosis was positively associated with MMP-9, P-selectin, and sPD-L1 and clinically related to a worse outcome. This is the first study associating NETs with a worse outcome in MPE. Neutrophils likely contribute to tumor progression through the release of NETs, suggesting that they are a potential therapeutic target in LAC.MDPI2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11252https://ddd.uab.cat/record/284180CancersISSN: 20726694reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p112522026-06-14T12:41:47Z
dc.title.none.fl_str_mv Influence of Malignant Pleural Fluid from Lung Adenocarcinoma Patients on Neutrophil Response
title Influence of Malignant Pleural Fluid from Lung Adenocarcinoma Patients on Neutrophil Response
spellingShingle Influence of Malignant Pleural Fluid from Lung Adenocarcinoma Patients on Neutrophil Response
Mulet, M
malignant pleural fluid
lung adenocarcinoma
neutrophils
NETosis
title_short Influence of Malignant Pleural Fluid from Lung Adenocarcinoma Patients on Neutrophil Response
title_full Influence of Malignant Pleural Fluid from Lung Adenocarcinoma Patients on Neutrophil Response
title_fullStr Influence of Malignant Pleural Fluid from Lung Adenocarcinoma Patients on Neutrophil Response
title_full_unstemmed Influence of Malignant Pleural Fluid from Lung Adenocarcinoma Patients on Neutrophil Response
title_sort Influence of Malignant Pleural Fluid from Lung Adenocarcinoma Patients on Neutrophil Response
dc.creator.none.fl_str_mv Mulet, M
Osuna-Gomez, R
Zamora, C
Porcel, JM
Nieto, JC
Perea, L
Pajares, V
Munoz-Fernandez, AM
Calvo, N
Sorolla, MA
Vidal, S
author Mulet, M
author_facet Mulet, M
Osuna-Gomez, R
Zamora, C
Porcel, JM
Nieto, JC
Perea, L
Pajares, V
Munoz-Fernandez, AM
Calvo, N
Sorolla, MA
Vidal, S
author_role author
author2 Osuna-Gomez, R
Zamora, C
Porcel, JM
Nieto, JC
Perea, L
Pajares, V
Munoz-Fernandez, AM
Calvo, N
Sorolla, MA
Vidal, S
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv malignant pleural fluid
lung adenocarcinoma
neutrophils
NETosis
topic malignant pleural fluid
lung adenocarcinoma
neutrophils
NETosis
description Simple Summary This study provides novel information about the role of neutrophils in malignant pleural effusion (MPE) and hallmarks their clinical relevance. Since these cells have emerged as important regulators of cancer, we characterized their phenotype and functions in MPE microenvironment. We found that neutrophil-derived products (degranulation molecules and neutrophil extracellular traps (NETs)) were increased in MPE. In addition, NETs were associated with a worse outcome in lung adenocarcinoma patients with MPE. Malignant pleural effusion (MPE) is a common severe complication of advanced lung adenocarcinoma (LAC). Neutrophils, an essential component of tumor infiltrates, contribute to tumor progression and their counts in MPE have been associated with worse outcome in LAC. This study aimed to evaluate phenotypical and functional changes of neutrophils induced by MPE to determine the influence of MPE immunomodulatory factors in neutrophil response and to find a possible association between neutrophil functions and clinical outcomes. Pleural fluid samples were collected from 47 LAC and 25 heart failure (HF) patients. We measured neutrophil degranulation products by ELISA, oxidative burst capacity and apoptosis by flow cytometry, and NETosis by fluorescence. The concentration of degranulation products was higher in MPE-LAC than in PE-HF. Functionally, neutrophils cultured with MPE-LAC had enhanced survival and neutrophil extracellular trap (NET) formation but had reduced oxidative burst capacity. In MPE, NETosis was positively associated with MMP-9, P-selectin, and sPD-L1 and clinically related to a worse outcome. This is the first study associating NETs with a worse outcome in MPE. Neutrophils likely contribute to tumor progression through the release of NETs, suggesting that they are a potential therapeutic target in LAC.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11252
https://ddd.uab.cat/record/284180
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11252
https://ddd.uab.cat/record/284180
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Cancers
ISSN: 20726694
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
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