TRIM21-mediated degradation of HILPDA overcomes anti-PD-1 immunotherapy resistance in breast cancer by limiting PD-L1 palmitoylation - PubMed
2 months ago
- #PD-L1 palmitoylation
- #breast cancer
- #immunotherapy resistance
- HILPDA被确定为乳腺癌中肿瘤内在免疫逃逸的调控因子
- HILPDA过表达增加调节性T细胞，减少CD8+ T细胞和自然杀伤细胞，形成免疫抑制性肿瘤微环境
- HILPDA与HSP90结合，保护KLF5免于降解，维持脂肪酸合成和脂滴积累
- 棕榈酸酯增加促进PD-L1棕榈酰化，稳定PD-L1并维持抑制性信号传导
- TRIM21介导HILPDA的K63连接多聚泛素化，促进其降解
- 芬维A胺通过激活TRIM21减少PD-L1棕榈酰化，重编程肿瘤微环境并增强抗PD-1疗效
- 靶向TRIM21/HILPDA的联合疗法被提出作为克服免疫检查点抑制剂耐药的治疗策略