DPP9 inhibition boosts antitumor immunity by disrupting BRISC-mediated PD-L1 expression in clear cell renal cell carcinoma - PubMed
4 hours ago
- #immunotherapy
- #renal cell carcinoma
- #PD-L1 regulation
- DPP9 inhibition enhances antitumor immunity by disrupting BRISC-mediated PD-L1 expression in clear cell renal cell carcinoma (ccRCC).
- DPP9 inhibitor 1G244 restores T cell cytotoxicity and improves checkpoint blockade efficacy by reducing PD-L1 levels.
- DPP9 disrupts the BRISC-SHMT2 complex, stabilizing IFNAR1 and activating the JAK/STAT pathway to drive PD-L1 transcription.
- 1G244 reduces DPP9 interaction with SHMT2, promoting IFNAR1 degradation and lowering PD-L1 expression.
- Combination therapy of 1G244 and anti-CTLA-4 enhances antitumor immunity, suggesting a potential synergistic treatment strategy.
- The study identifies the DPP9-BRISC-SHMT2 axis as a novel regulatory mechanism for PD-L1 expression in ccRCC.