CTHRC1 drives megakaryocyte-mediated immunotherapy resistance in esophageal squamous cell carcinoma via the integrin αIIbβ3/Rap1 pathway and is targetable by mRNA vaccination - PubMed
3 hours ago
- #Immunotherapy Resistance
- #mRNA Vaccine
- #Tumor Microenvironment
- CTHRC1 is identified as a key factor causing immunotherapy resistance in esophageal squamous cell carcinoma (ESCC) by promoting megakaryocyte activity and recruitment.
- High CTHRC1 levels correlate with poor response to immune checkpoint blockade, leading to an immunosuppressive environment that reduces T-cell effectiveness.
- An mRNA vaccine targeting CTHRC1, delivered via lipid nanoparticles, was developed and showed strong anti-tumor effects in preclinical ESCC models.
- Combining the CTHRC1 mRNA vaccine with anti-PD-1 therapy enhanced T-cell infiltration, reduced megakaryocytes, and reversed immunosuppression, resulting in lasting tumor regression.