Title:Tumor-Activated Neutrophils Promote Lung Cancer Progression through
the IL-8/PD-L1 Pathway
Volume: 25
Issue: 3
Author(s): Yiping Zheng, Jianfeng Cai, Qiuhong Ji, Luanmei Liu, Kaijun Liao, Lie Dong, Jie Gao and Yinghui Huang*
Affiliation:
- Department of Respiratory and Critical Care Medicine, Nanping First Hospital Affiliated to Fujian Medical University,
Nanping, Fujian, 353006, China
Keywords:
Lung cancer, neutrophils, IL-8, PD-L1, immune escape, tumor microenvironment.
Abstract:
Background: Lung cancer remains a major global health threat due to its complex microenvironment,
particularly the role of neutrophils, which are crucial for tumor development and
immune evasion mechanisms. This study aimed to delve into the impact of lung cancer cell-conditioned
media on neutrophil functions and their potential implications for lung cancer progression.
Methods: Employing in vitro experimental models, this study has analyzed the effects of lung cancer
cell-conditioned media on neutrophil IL-8 and IFN-γ secretion, apoptosis, PD-L1 expression,
and T-cell proliferation by using techniques, such as ELISA, flow cytometry, immunofluorescence,
and CFSE proliferation assay. The roles of IL-8/PD-L1 in regulating neutrophil functions
were further explored using inhibitors for IL-8 and PD-L1.
Results: Lung cancer cell lines were found to secrete higher levels of IL-8 compared to normal
lung epithelial cells. The conditioned media from lung cancer cells significantly reduced apoptosis
in neutrophils, increased PD-L1 expression, and suppressed T-cell proliferation and IFN-γ secretion.
These effects were partially reversed in the presence of IL-8 inhibitors in Tumor Tissue Culture
Supernatants (TTCS), while being further enhanced by IL-8. Both apoptosis and PD-L1 expression
in neutrophils demonstrated dose-dependency to TTCS. Additionally, CFSE proliferation
assay results further confirmed the inhibitory effect of lung cancer cell-conditioned media on T--
cell proliferation.
Conclusion: This study has revealed lung cancer cell-conditioned media to modulate neutrophil
functions through regulating factors, such as IL-8, thereby affecting immune regulation and tumor
progression in the lung cancer microenvironment.
