Your browser doesn't support javascript.
loading
Regorafenib enhances anti-tumor efficacy of immune checkpoint inhibitor by regulating IFN-γ/NSDHL/SREBP1/TGF-ß1 axis in hepatocellular carcinoma.
Xie, Lulu; Liu, Mingyu; Cai, Mingyue; Huang, Wensou; Guo, Yongjian; Liang, Licong; Cai, Weiguo; Liu, Jianxin; Liang, Wei; Tan, Yitong; Lai, Miaoling; Lin, Liteng; Zhu, Kangshun.
Afiliación
  • Xie L; Laboratory of Interventional Radiology, Department of Minimally Invasive Interventional Radiology and Radiology Center, and Minimally Invasive and Interventional Cancer Center, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 510260,
  • Liu M; Laboratory of Interventional Radiology, Department of Minimally Invasive Interventional Radiology and Radiology Center, and Minimally Invasive and Interventional Cancer Center, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 510260,
  • Cai M; Laboratory of Interventional Radiology, Department of Minimally Invasive Interventional Radiology and Radiology Center, and Minimally Invasive and Interventional Cancer Center, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 510260,
  • Huang W; Laboratory of Interventional Radiology, Department of Minimally Invasive Interventional Radiology and Radiology Center, and Minimally Invasive and Interventional Cancer Center, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 510260,
  • Guo Y; Laboratory of Interventional Radiology, Department of Minimally Invasive Interventional Radiology and Radiology Center, and Minimally Invasive and Interventional Cancer Center, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 510260,
  • Liang L; Laboratory of Interventional Radiology, Department of Minimally Invasive Interventional Radiology and Radiology Center, and Minimally Invasive and Interventional Cancer Center, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 510260,
  • Cai W; Laboratory of Interventional Radiology, Department of Minimally Invasive Interventional Radiology and Radiology Center, and Minimally Invasive and Interventional Cancer Center, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 510260,
  • Liu J; Laboratory of Interventional Radiology, Department of Minimally Invasive Interventional Radiology and Radiology Center, and Minimally Invasive and Interventional Cancer Center, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 510260,
  • Liang W; Laboratory of Interventional Radiology, Department of Minimally Invasive Interventional Radiology and Radiology Center, and Minimally Invasive and Interventional Cancer Center, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 510260,
  • Tan Y; Laboratory of Interventional Radiology, Department of Minimally Invasive Interventional Radiology and Radiology Center, and Minimally Invasive and Interventional Cancer Center, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 510260,
  • Lai M; Department of Pathology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 510260, China.
  • Lin L; Laboratory of Interventional Radiology, Department of Minimally Invasive Interventional Radiology and Radiology Center, and Minimally Invasive and Interventional Cancer Center, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 510260,
  • Zhu K; Laboratory of Interventional Radiology, Department of Minimally Invasive Interventional Radiology and Radiology Center, and Minimally Invasive and Interventional Cancer Center, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 510260,
Biomed Pharmacother ; 159: 114254, 2023 Mar.
Article en En | MEDLINE | ID: mdl-36669362
ABSTRACT
Immune checkpoint inhibitor (ICI) shows low response rate in hepatocellular carcinoma (HCC) but the mechanisms underlying ICI resistance remains unclear. Interferon-γ (IFN-γ) has been widely determined as a prototypical antitumor cytokine. However, growing studies suggest that IFN-γ also mediates immunosuppression to promote tumor progression. Herein, we explored whether ICI-induced IFN-γ could activate immunosuppressive TGF-ß1 to mediate ICI resistance. We demonstrated that cholesterol biosynthetic enzyme, NSDHL, was decreased in HCC tissues and associated with poor clinical prognosis. ICI-induced IFN-γ decreased NSDHL to activate SREBP1, which promoted TGF-ß1 production, reduced T cell toxicity and enhanced Tregs infiltration, leading to ICI resistance. We also found that novel tyrosine kinase inhibitor, regorafenib, significantly reverse the above immunosuppressive effects by regulating NSDHL/SREBP1/TGF-ß1 axis, which strengthened the effects of regorafenib plus ICI therapy against HCC. Noteworthily, regorafenib plus ICI therapy was more effective in HCC patients with higher serum TGF-ß1. In conclusion, IFN-γ induced TGF-ß1 to mediate ICI resistance. Regorafenib promotes anti-tumor immune response of ICI by regulating IFN-γ/NSDHL/SREBP1/TGF-ß1 axis. Serum TGF-ß1 may serve as a biomarker for predicting efficacy of regorafenib plus ICI therapy in HCC.
Asunto(s)
Palabras clave
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Biomed Pharmacother Año: 2023 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Biomed Pharmacother Año: 2023 Tipo del documento: Article