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

Maria Mulet1, Rubén Osuna-Gómez1, Carlos Zamora1

  • 1Inflammatory Diseases, Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain.

Cancers
|May 28, 2022
PubMed

Insights

Malignant pleural effusions in lung adenocarcinoma promote neutrophil extracellular trap (NET) formation, which is linked to worse patient outcomes. Targeting NETs may offer a new therapeutic strategy for advanced lung cancer.

Area of Science:

  • Oncology
  • Immunology
  • Pulmonology

Background:

  • Malignant pleural effusion (MPE) is a severe complication of advanced lung adenocarcinoma (LAC).
  • Neutrophils in tumor infiltrates can drive tumor progression.
  • Elevated neutrophil counts in MPE correlate with poor prognosis in LAC.

Purpose of the Study:

  • To investigate phenotypical and functional alterations in neutrophils exposed to MPE.
  • To assess the impact of MPE immunomodulatory factors on neutrophil responses.
  • To explore associations between neutrophil functions and clinical outcomes in LAC patients.

Main Methods:

  • Collected pleural fluid from 47 LAC patients and 25 heart failure (HF) patients.
  • Quantified neutrophil degranulation products using ELISA.
  • Assessed neutrophil oxidative burst, apoptosis, and NETosis via flow cytometry and fluorescence microscopy.

Main Results:

  • Neutrophils in MPE-LAC showed increased survival and neutrophil extracellular trap (NET) formation compared to PE-HF.
  • Oxidative burst capacity was reduced in neutrophils cultured with MPE-LAC.
  • NETosis positively correlated with MMP-9, P-selectin, and sPD-L1, and was associated with worse clinical outcomes.

Conclusions:

  • This study establishes a link between NETosis and poor prognosis in MPE-associated LAC.
  • Neutrophils, via NET release, may actively contribute to tumor progression in MPE.
  • NETs represent a potential therapeutic target for advanced lung adenocarcinoma.