ChemoNETosis in Cancer: A Comprehensive Review of Treatment-Induced NET Formation and Therapeutic Consequences

Area of Science:

• Immunology
• Oncology
• Cell Biology

Background:

• ChemoNETosis is a distinct therapy-induced innate immune activation.
• Cytotoxic chemotherapy alters the tumor microenvironment (TME), attracting neutrophils and triggering neutrophil extracellular traps (NETs).
• Unlike classical NETosis, chemoNETosis is initiated by treatment-related signals and chemokine-cytokine loops.

Purpose of the Study:

• To provide the first in-depth synthesis of chemoNETosis across solid tumors.
• To focus on key mechanistic nodes of chemoNETosis.
• To explore translational perspectives of chemoNETosis.

Main Methods:

• Review of existing literature on chemoNETosis.
• Analysis of mechanistic nodes driving chemoNETosis.
• Synthesis of translational perspectives for chemoNETosis.

Main Results:

• ChemoNETosis promotes NET-rich metastatic niches by serving as scaffolds and bioactive platforms.
• NET structures drive epithelial-mesenchymal transition, tumor cell plasticity, immune exclusion, and chemotherapy resistance.
• ChemoNETosis can exhibit context-dependent plasticity, potentially contributing to antitumor responses under specific conditions.

Conclusions:

• ChemoNETosis is a significant factor in cancer progression and treatment resistance.
• Understanding chemoNETosis mechanisms is crucial for developing novel cancer therapies.
• Targeting chemoNETosis may offer new therapeutic strategies for solid tumors.