Extracellular vesicles from the lung pro-thrombotic niche drive cancer-associated thrombosis and metastasis via integrin beta 2.
Summary
This study identifies a lung 'pro-thrombotic niche' where CXCL13-reprogrammed interstitial macrophages secrete small EVs carrying clustered integrin β2, which promote thrombosis and metastasis. It mechanistically links lung microenvironment-derived EVs to systemic thromboinflammation in cancer, highlighting ITGB2 and CXCL13 axes as therapeutic targets.
Key Findings
- Defined a lung 'pro-thrombotic niche' consisting of CXCL13-reprogrammed interstitial macrophages secreting pro-thrombotic sEVs.
- sEVs carried clustered integrin β2, mechanistically linking EV cargo to platelet/immune activation, thrombosis, and metastasis.
- Findings generalize across multiple cancers with non-metastatic lung microenvironments, indicating a systemic role of lung-derived EVs.
Clinical Implications
Suggests potential for anti-integrin β2 or CXCL13 pathway modulation to reduce cancer-associated thrombosis and possibly metastasis. May inform biomarker development using EV cargo for thrombotic risk stratification.
Why It Matters
Reveals a previously unrecognized lung-derived EV mechanism that connects thrombosis to metastasis and provides tractable targets (integrin β2, CXCL13) for intervention. High translational relevance across cancers with thrombotic complications.
Limitations
- Predominantly preclinical mechanistic evidence; interventional validation in humans is needed
- Details of human cohort validation and causal therapeutics are not established in this report
Future Directions
Develop anti-ITGB2 or anti-CXCL13 strategies; validate EV-based biomarkers of thrombotic risk; test whether modulating the lung PTN reduces thrombosis/metastasis clinically.
Study Information
- Study Type
- Case series
- Research Domain
- Pathophysiology
- Evidence Level
- IV - Mechanistic/translational evidence with preclinical and limited human sample analyses
- Study Design
- OTHER