Abstract 82P
Background
Neutrophil extracellular traps (NETs) are involved in the progression and metastasis of a variety of malignancies. Our previous studies have confirmed that tumor cell-released autophagosomes (TRAPs) induced immunosuppression TME formation. However, it remains to be investigated whether TRAPs-treated neutrophils contribute to the metastatic colonization of the lungs by tumor cells.To explore TRAPs induced neutrophils to form NETs and its regulatory mechanism of tumor metastasis, providing possible targets for disease treatment.
Methods
NETs were observed by scanning electron microscopy (SEM) and Confocal Microscope. Western blot and ELISA were used to quantify MPO-DNA, NE, and cit-H3 which are important components of NETs. In vivo, TRAPs were injected into the tail vein of mice and Beclin1 knockdown 4T1 tumor cells engineering to reduce TRAPs release were injected into mice subcutaneously. The characteristic molecules of NETs in plasma were detected. The study used antibody blocking assays to identify key DAMPs on the surface of TRAPs. Flow cytometry was used to evaluate T cell and lung infiltrating T cell function, as well as to monitor late lung metastases in neutrophils treated with TRAPs suppressor.
Results
Numerous reticular structures significantly increased in the cell culture supernatant after TRAPs treatment. In vivo, NETs were significantly increased in plasma after tail vein injection of TRAPs as well as in 4T1 tumor-bearing mice. Conversely, NETs were significantly decreased in the plasma of Beclin1 knockdown 4T1 tumor-bearing mice. TRAPs derived from breast tumor cell lines induced neutrophil formation of NETs via the HMGB1-TLR4-MyD88-ERK/p38 pathway. This process inhibited the proliferation and secretion of IFN-γ in CD4+ and CD8+ T cells, ultimately leading to increased lung metastasis.
Conclusions
TRAPs promote breast cancer lung metastasis by modulating neutrophil extracellular traps formation. Overall, these findings define a novel mechanism mediated by TRAPs in neutrophils, which may suppress anti-tumor T cell immunity and highlight TRAPs as an important target for future tumor immunotherapy.
Editorial acknowledgement
Clinical trial identification
Legal entity responsible for the study
Chengdong Wu, Xuru Wang.
Funding
The National Natural Science Foundation of China.
Disclosure
The author has declared no conflicts of interest.
Resources from the same session
136P - Molecular correlates of drug response to guide therapy in TNBC
Presenter: Nathan Merrill
Session: Cocktail & Poster Display session
Resources:
Abstract
137P - Event-free survival prediction using lncRNAs in pediatric B-cell acute lymphoblastic leukemia
Presenter: Unai Illarregi
Session: Cocktail & Poster Display session
Resources:
Abstract
138P - Exome sequencing analysis for the identification of actionable mutations related to neoadjuvant chemotherapy response in locally advanced breast cancer
Presenter: Ximena López
Session: Cocktail & Poster Display session
Resources:
Abstract
139P - Genomic prognostic and potential theragnostic factors in anal squamous cell carcinoma treated with abdominoperineal resection
Presenter: Abderaouf Hamza
Session: Cocktail & Poster Display session
Resources:
Abstract
144P - Correlation of EZH2 expression and response to chemoradiotherapy in patients with locally advanced inoperable oral cavity and oropharyngeal squamous cell cancers
Presenter: Soel Ahmed
Session: Cocktail & Poster Display session
Resources:
Abstract
140P - Predictive value of DNA damage response and repair gene alterations and neoscore for neoadjuvant immunotherapies in non-small cell lung cancer
Presenter: Fei Feng
Session: Cocktail & Poster Display session
Resources:
Abstract
141P - Immune-related epigenomic and transcriptomic signatures to predict immunotherapy response in NSCLC
Presenter: María Gallardo-Gómez
Session: Cocktail & Poster Display session
Resources:
Abstract
142P - Role and impact of hypoxia-inducible factor 1-alpha on survival rates in pancreatic cancer: A systematic review and meta-analysis
Presenter: Muhammed Elfaituri
Session: Cocktail & Poster Display session
Resources:
Abstract
143P - Genomic characterization and outcomes of patients with primary sclerosing cholangitis-related cholangiocarcinoma
Presenter: Jaime Haro Silerio
Session: Cocktail & Poster Display session
Resources:
Abstract
145P - Identification of next generation sequencing (NGS)-based genomic signature predicting resistance to immunotherapy (IO) in patients (pts) with metastatic non-small cell lung cancer (mNSCLC): A single-center cohort study
Presenter: Antonio Vitale
Session: Cocktail & Poster Display session
Resources:
Abstract