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Isolation and Characterization of Neutrophils with Anti-Tumor Properties
Published on: June 19, 2015
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Unique pattern of neutrophil migration and function during tumor progression
Sima Patel1,2, Shuyu Fu1,3, Jerome Mastio1
1Immunology, Microenvironment, and Metastasis, Wistar Institute, Philadelphia, PA, USA.
Nature Immunology
|October 17, 2018
Summary
Neutrophils from early-stage cancer exhibit enhanced spontaneous migration via ATP signaling, contributing to tumor spread. Later-stage cancer neutrophils lose this migratory ability, showing dynamic changes in cancer progression.
Area of Science:
- Immunology
- Cancer Biology
- Cellular Metabolism
Background:
- Neutrophils are implicated in pre-metastatic niche formation, but their migration mechanisms to distant sites are unclear.
- Understanding neutrophil behavior is crucial for deciphering early tumor dissemination.
Purpose of the Study:
- To elucidate the mechanism behind neutrophil migration to distant tissues in early-stage cancer.
- To investigate the metabolic and functional changes in neutrophils during cancer progression.
Main Methods:
- Comparative analysis of bone marrow neutrophils from early-stage cancer mice versus tumor-free mice.
- Assessment of neutrophil migration, oxidative phosphorylation, glycolysis, ATP production, and immunosuppressive activity.
- Investigation using ectopic tumor models and analysis of neutrophils from cancer patients.
Main Results:
- Early-stage cancer neutrophils display heightened spontaneous migration, increased ATP production, and elevated oxidative phosphorylation and glycolysis.
- This enhanced migration is driven by autocrine ATP signaling via purinergic receptors.
- Neutrophils from late-stage cancer and cancer patients exhibit potent immunosuppression but lack enhanced migratory activity.
Conclusions:
- Neutrophil function dynamically changes during cancer progression, with early-stage cells promoting dissemination.
- Autocrine ATP signaling is a key mechanism for neutrophil migration in early cancer.
- These findings reveal a novel mechanism for neutrophil involvement in early tumor spread.
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