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

5 days ago
  • #Immunotherapy
  • #FGFR1
  • #Hepatocellular Carcinoma
  • Targeting FGFR1-regulated SPP1 signaling repolarizes immunosuppressive macrophages and sensitizes Hepatocellular Carcinoma (HCC) to anti-PD-1 therapy.
  • ICB resistance in HCC is associated with FGFR1 upregulation, activating MAPK signaling and inducing SPP1 expression, promoting M2-type macrophage polarization and suppressing T cell function.
  • SPP1 knockdown or neutralization reduces macrophage accumulation and restores T cell infiltration in tumors.
  • Pharmacological inhibition of FGFR1 with BGJ398 synergizes with anti-PD-1 therapy, enhancing antitumor efficacy in preclinical models.
  • High FGFR1 expression correlates with poor responses to ICB in HCC patients, suggesting FGFR1 as a predictive biomarker.