Influence of Malignant Pleural Fluid from Lung Adenocarcinoma Patients on Neutrophil Response
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 pheno...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/10/2529 |
| _version_ | 1797500983240032256 |
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| author | Maria Mulet Rubén Osuna-Gómez Carlos Zamora José M. Porcel Juan C. Nieto Lídia Perea Virginia Pajares Ana M. Muñoz-Fernandez Nuria Calvo Maria Alba Sorolla Silvia Vidal |
| author_facet | Maria Mulet Rubén Osuna-Gómez Carlos Zamora José M. Porcel Juan C. Nieto Lídia Perea Virginia Pajares Ana M. Muñoz-Fernandez Nuria Calvo Maria Alba Sorolla Silvia Vidal |
| author_sort | Maria Mulet |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T03:11:43Z |
| format | Article |
| id | doaj.art-89af8c611bbf4860ad8fffe3e82283fa |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T03:11:43Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-89af8c611bbf4860ad8fffe3e82283fa2023-11-23T10:24:26ZengMDPI AGCancers2072-66942022-05-011410252910.3390/cancers14102529Influence of Malignant Pleural Fluid from Lung Adenocarcinoma Patients on Neutrophil ResponseMaria Mulet0Rubén Osuna-Gómez1Carlos Zamora2José M. Porcel3Juan C. Nieto4Lídia Perea5Virginia Pajares6Ana M. Muñoz-Fernandez7Nuria Calvo8Maria Alba Sorolla9Silvia Vidal10Inflammatory Diseases, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, SpainInflammatory Diseases, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, SpainInflammatory Diseases, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, SpainPleural Medicine Unit, Department of Internal Medicine, Hospital Universitari Arnau de Vilanova, IRBLleida, University of Lleida, 25003 Lleida, SpainInflammatory Diseases, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, SpainInflammatory Diseases, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, SpainDepartment of Pneumology, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, SpainDepartment of Pneumology, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, SpainDepartment of Oncology, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, SpainResearch Group of Cancer Biomarkers, IRBLleida, 25198 Lleida, SpainInflammatory Diseases, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, SpainMalignant 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.https://www.mdpi.com/2072-6694/14/10/2529malignant pleural fluidlung adenocarcinomaneutrophilsNETosis |
| spellingShingle | Maria Mulet Rubén Osuna-Gómez Carlos Zamora José M. Porcel Juan C. Nieto Lídia Perea Virginia Pajares Ana M. Muñoz-Fernandez Nuria Calvo Maria Alba Sorolla Silvia Vidal Influence of Malignant Pleural Fluid from Lung Adenocarcinoma Patients on Neutrophil Response Cancers malignant pleural fluid lung adenocarcinoma neutrophils NETosis |
| title | 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_short | 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 |
| topic | malignant pleural fluid lung adenocarcinoma neutrophils NETosis |
| url | https://www.mdpi.com/2072-6694/14/10/2529 |
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