Neutrophil Spatiotemporal Regulatory Networks: Dual Roles in Tumor Growth Regulation and Metastasis

Area of Science:

• Oncology
• Immunology
• Cell Biology

Background:

• Neutrophils are abundant leukocytes with significant plasticity in tumor biology.
• Their function can be anti-tumor or pro-tumor, depending on the tumor microenvironment.
• Neutrophils are implicated in tumor initiation, progression, and metastasis.

Purpose of the Study:

• To provide a comprehensive synthesis of neutrophil-mediated mechanisms in the tumor microenvironment.
• To highlight emerging strategies for neutrophil-targeted cancer therapy.

Main Methods:

• Review of existing literature on neutrophil roles in cancer.
• Analysis of neutrophil functions including polarization, mediator secretion, NET formation, and ROS/RNS production.
• Examination of neutrophil involvement in epithelial-mesenchymal transition (EMT), pre-metastatic niche formation, and tumor cell dormancy reactivation.

Main Results:

• Neutrophils promote genomic instability during tumor initiation via cytokine and microRNA secretion.
• During progression, neutrophils polarize into N1 (anti-tumor) or N2 (pro-tumor) subsets and modulate the tumor microenvironment.
• Neutrophils facilitate metastasis through EMT promotion, pre-metastatic niche establishment, and reactivation of dormant tumor cells.

Conclusions:

• Neutrophils are central regulators across all stages of tumor evolution, impacting cancer growth, immune evasion, and metastasis.
• Targeting neutrophil functions presents a promising avenue for novel cancer therapies.