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Synergistic effect of IFN-γ and IL-1β on PD-L1 expression in hepatocellular carcinoma

Immunotherapy using anti-programmed death 1 ligand 1 (PD-L1) antibodies has shown clinical efficacy against hepatocellular carcinoma (HCC) and is recognized as the first-line treatment for unresectable HCC. PD-L1 expression is affected by various cytokines produced by immune cells in the tumor micro...

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Detalles Bibliográficos
Autores principales: Numata, Yasunao, Akutsu, Noriyuki, Ishigami, Keisuke, Koide, Hideyuki, Wagatsuma, Kohei, Motoya, Masayo, Sasaki, Shigeru, Nakase, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9095738/
https://www.ncbi.nlm.nih.gov/pubmed/35573813
http://dx.doi.org/10.1016/j.bbrep.2022.101270
Descripción
Sumario:Immunotherapy using anti-programmed death 1 ligand 1 (PD-L1) antibodies has shown clinical efficacy against hepatocellular carcinoma (HCC) and is recognized as the first-line treatment for unresectable HCC. PD-L1 expression is affected by various cytokines produced by immune cells in the tumor microenvironment; however, there is limited information about the effects of cytokine interactions on PD-L1 expression. In this study, we examined how cytokines induce PD-L1 expression in HCC cells. Both interferon gamma (IFN-γ) and interleukin 1 beta (IL-1β) induced PD-L1 expression, and the two cytokines enhanced PD-L1 expression in combination compared to that when administered alone. The Janus kinase/signal transducer and activator of transcription signaling pathway activated by IFN-γ is the major pathway of PD-L1 expression. The increase in interferon regulatory factor 1 expression and IFN-γ receptor expression induced by IL-1β was associated with the synergistic effect of IFN-γ and IL-1β on PD-L1 expression. These findings strongly indicate that IFN-γ and IL-1β affect the mechanism underlying immune resistance in HCC cells.