Telmisartan increases olaparib efficacy in homologous recombination proficient tumors by augmenting type I interferon production - PubMed
5 hours ago
- #Telmisartan
- #PARP inhibitor
- #Type I interferon
- PARP inhibitors (PARPi) are effective in treating tumors deficient in homologous recombination (HR), but mechanisms in BRCA wild-type tumors are unclear.
- Telmisartan, an angiotensin II receptor blocker (ARB), depletes tumor PD-L1 and synergizes with olaparib (a PARPi) to increase DNA damage and efficacy.
- The synergy occurs independently of tumor PD-L1, expanding telmisartan's applicability to PD-L1-negative tumors.
- Telmisartan is unique among ARBs tested in depleting PD-L1 and enhancing PARPi effects, not a class-wide effect.
- Combining telmisartan with PARPi increases cytosolic DNA and STING signaling, boosting type I interferon (IFN-I) production.
- In vivo, telmisartan improves PARPi efficacy, but efficacy is lost if tumor STING or IFN-I signals are eliminated.
- IFN-I blockade reduces antitumor immunity, indicating STING-induced IFN-I as a key mechanism for enhanced immunity in combination therapy.
- Telmisartan has clinical potential to improve PARPi in BRCA wild-type tumors and enhance tumor immunogenicity.