Influence of Malignant Pleural Fluid from Lung Adenocarcinoma Patients on Neutrophil Response
Por:
Mulet, M, Osuna-Gomez, R, Zamora, C, Porcel, JM, Nieto, JC, Perea, L, Pajares, V, Munoz-Fernandez, AM, Calvo, N, Sorolla, MA, Vidal, S
Publicada:
1 may 2022
Resumen:
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.
Filiaciones:
Mulet, M:
Hosp Santa Creu & Sant Pau, Inflammatory Dis, Inst Recerca, Biomed Res Inst St Pau IIB St Pau, Barcelona 08041, Spain
Osuna-Gomez, R:
Hosp Santa Creu & Sant Pau, Inflammatory Dis, Inst Recerca, Biomed Res Inst St Pau IIB St Pau, Barcelona 08041, Spain
Zamora, C:
Hosp Santa Creu & Sant Pau, Inflammatory Dis, Inst Recerca, Biomed Res Inst St Pau IIB St Pau, Barcelona 08041, Spain
Porcel, JM:
Univ Lleida, Hosp Univ Arnau de Vilanova, Dept Internal Med, IRBLleida,Pleural Med Unit, Lleida 25003, Spain
Nieto, JC:
Hosp Santa Creu & Sant Pau, Inflammatory Dis, Inst Recerca, Biomed Res Inst St Pau IIB St Pau, Barcelona 08041, Spain
Perea, L:
Hosp Santa Creu & Sant Pau, Inflammatory Dis, Inst Recerca, Biomed Res Inst St Pau IIB St Pau, Barcelona 08041, Spain
Pajares, V:
Hosp Santa Creu & Sant Pau, Dept Pneumol, Barcelona 08041, Spain
Munoz-Fernandez, AM:
Hosp Santa Creu & Sant Pau, Dept Pneumol, Barcelona 08041, Spain
Calvo, N:
Hosp Santa Creu & Sant Pau, Dept Oncol, Barcelona 08041, Spain
Sorolla, MA:
IRBLleida, Res Grp Canc Biomarkers, Lleida 25198, Spain
Vidal, S:
Hosp Santa Creu & Sant Pau, Inflammatory Dis, Inst Recerca, Biomed Res Inst St Pau IIB St Pau, Barcelona 08041, Spain
gold, Green Published, All Open Access, Gold, Green
|