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Targeting FGFR1-regulated SPP1 signaling repolarizes immunosuppressive macrophages and sensitizes Hepatocellular Carcinoma to anti-PD-1 therapy - PubMed

2 months ago
  • #Immunotherapy
  • #FGFR1
  • #Hepatocellular Carcinoma
  • 靶向FGFR1调控的SPP1信号通路可重编程免疫抑制性巨噬细胞,使肝细胞癌(HCC)对抗PD-1治疗敏感化
  • HCC对免疫检查点抑制剂(ICB)的耐药性与FGFR1上调相关,其通过激活MAPK信号通路诱导SPP1表达,促进M2型巨噬细胞极化并抑制T细胞功能
  • 敲除或中和SPP1可减少肿瘤中巨噬细胞浸润并恢复T细胞聚集
  • FGFR1抑制剂BGJ398与抗PD-1疗法具有协同作用,在临床前模型中显著增强抗肿瘤效果
  • HCC患者中FGFR1高表达与ICB治疗应答率低显著相关,提示FGFR1可作为预测性生物标志物