Neutrophils in advanced non-small cell lung cancer
type: CreativeWork
description: Lung cancer is the third most common cancer in the UK; 87% are histologically nonsmall cell lung cancer (NSCLC). At the time of diagnosis, patients frequently have advanced disease, with poor one-year survival due to metastatic burden. The immune system should act as a key line of defence; recognising, killing and clearing malignant cells. However, ineffective immune responses contribute to cancer progression. Neutrophils are active players in the metastatic environment, but there is limited data regarding human neutrophil populations in advanced lung cancer. Greater understanding of the interplay between extrinsic cell signals and intrinsic cell features in determining neutrophil roles, is also needed. In this study, to investigate how the extrinsic metastatic NSCLC pleural environment influences the function of neutrophils, it was modelled in vitro by culturing healthy donor neutrophils in conditions emulating the pleural space. Tumour necrosis factor alpha (TNFa) and hypoxia acted as pro-survival signals leading to neutrophil persistence and NSCLC pleural fluid conditioned neutrophils to suppress CD8+ T cells through mechanisms including programmed death-ligand 1 (PD-L1) expression. To establish the phenotype of neutrophil populations in advanced NSCLC, neutrophils were extracted from the pleural fluid (metastatic site) and blood of patients. Cellular morphology, surface marker expression and functional assays were utilised. There was an expanded population of low-density blood neutrophils in advanced NSCLC, that were not present in health, and a proportion of which were immature with banded nuclei. Similar immature neutrophils were seen in NSCLC pleural fluid. NSCLC pleural fluid neutrophils expressed PD-L1 and were long-lived. To understand how cell-intrinsic features of neutrophil populations in advanced NSCLC may determine their role in cancer, the populations were defined by their transcriptomic and proteomic signatures. This provided evidence that implied N…
abstract: Lung cancer is the third most common cancer in the UK; 87% are histologically nonsmall cell lung cancer (NSCLC). At the time of diagnosis, patients frequently have advanced disease, with poor one-year survival due to metastatic burden. The immune system should act as a key line of defence; recognising, killing and clearing malignant cells. However, ineffective immune responses contribute to cancer progression. Neutrophils are active players in the metastatic environment, but there is limited data regarding human neutrophil populations in advanced lung cancer. Greater understanding of the interplay between extrinsic cell signals and intrinsic cell features in determining neutrophil roles, is also needed. In this study, to investigate how the extrinsic metastatic NSCLC pleural environment influences the function of neutrophils, it was modelled in vitro by culturing healthy donor neutrophils in conditions emulating the pleural space. Tumour necrosis factor alpha (TNFa) and hypoxia acted as pro-survival signals leading to neutrophil persistence and NSCLC pleural fluid conditioned neutrophils to suppress CD8+ T cells through mechanisms including programmed death-ligand 1 (PD-L1) expression. To establish the phenotype of neutrophil populations in advanced NSCLC, neutrophils were extracted from the pleural fluid (metastatic site) and blood of patients. Cellular morphology, surface marker expression and functional assays were utilised. There was an expanded population of low-density blood neutrophils in advanced NSCLC, that were not present in health, and a proportion of which were immature with banded nuclei. Similar immature neutrophils were seen in NSCLC pleural fluid. NSCLC pleural fluid neutrophils expressed PD-L1 and were long-lived. To understand how cell-intrinsic features of neutrophil populations in advanced NSCLC may determine their role in cancer, the populations were defined by their transcriptomic and proteomic signatures. This provided evidence that implied N…
author: Grecian, Robert John
language: en
keywords: non-small cell lung cancer, NSCLC, pleural fluid, neutrophils
date published: 2020-11-30
date modified: 2026-07-24T02:14:14Z
provider: University of Edinburgh
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: The University of Edinburgh

PropertyValue
property ID: Handle
value: https://hdl.handle.net/1842/37504

PropertyValue
property ID: DOI
value: 10.7488/era/788