The Tumor-Platelet-Immune Interface: Driving Metastasis, Pre-Metastatic Niche Formation, and Therapeutic Vulnerabilities

Highlights1. Platelet-leukocyte crosstalk promotes CTC survival, immune evasion, and pre-metastatic niche priming.2. NETosis facilitates metastatic progression by trapping CTCs and remodeling the extracellular matrix.3. Conventional anti-platelet and anti-inflammatory therapies incompletely target these interconnected pathways.4. Multi-stimuli-responsive nanoparticles and functionalized hydrogels allow spatiotemporally precise delivery of cytotoxic, anti-platelet, and immunomodulatory agents.5. Multi-modal network disruption integrates platelet, immune, and tumor targeting to limit metastatic seeding and disease progression.