DPP9 inhibition boosts antitumor immunity by disrupting BRISC-mediated PD-L1 expression in clear cell renal cell carcinoma - PubMed
2 months ago
- #immunotherapy
- #renal cell carcinoma
- #PD-L1 regulation
- DPP9抑制通过破坏BRISC介导的PD-L1表达增强肾透明细胞癌（ccRCC）的抗肿瘤免疫
- DPP9抑制剂1G244通过降低PD-L1水平恢复T细胞毒性并提升检查点阻断疗效
- DPP9破坏BRISC-SHMT2复合体，稳定IFNAR1并激活JAK/STAT通路以驱动PD-L1转录
- 1G244减少DPP9与SHMT2的相互作用，促进IFNAR1降解并降低PD-L1表达
- 1G244与抗CTLA-4联合治疗可增强抗肿瘤免疫，提示潜在的协同治疗策略
- 该研究确立了DPP9-BRISC-SHMT2轴作为ccRCC中PD-L1表达的新型调控机制