Exogenous Epstein-Barr virus nuclear antigen 1 induces ADAR1-driven tumor resistance against immunotherapy - PubMed
5 days ago
- #Epstein-Barr virus
- #RNA editing
- #Immunotherapy
- Immune checkpoint blockade (ICB) therapy faces limitations due to tumor resistance linked to suppressed interferon (IFN) signaling.
- Exogenous Epstein-Barr virus-encoded EBNA1 drives immunosuppression via enhanced ADAR1-mediated RNA editing.
- EBNA1 overexpression reduces CD8+ T-cell infiltration, inhibits IFN responses, polarizes macrophages toward M2 phenotype, and accelerates tumor growth.
- EBNA1 forms a trimeric complex with IGF2BP3 and EIF4G1, enhancing ADAR1 translation.
- Elevated ADAR1 increases A-to-I editing of dsRNA, masking immunostimulatory signals and impairing IFN pathways.
- Combining EBNA1-targeting PROTAC degrader EP-1215 with anti-PD-1 restores IFN signaling and suppresses EBNA1+ tumors in humanized mice.
- Targeting EBNA1 could convert 'cold' tumors into 'hot' targets for ICB therapy.