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

• Published in: Biochemistry and biophysics reports 2022-07, Vol.30, p.101270-101270, Article 101270
• Main Authors: Numata, Yasunao, Akutsu, Noriyuki, Ishigami, Keisuke, Koide, Hideyuki, Wagatsuma, Kohei, Motoya, Masayo, Sasaki, Shigeru, Nakase, Hiroshi
• Format: Article
• Language: English
• Subjects: Hepatocellular carcinoma; IFN-γ; IL-1β; PD-L1; Short Communication; Synergistic effect
• ISSN: 2405-5808; 2405-5808
• DOI: 10.1016/j.bbrep.2022.101270

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. •IFN-γ and IL-1β synergistically increase the expression of PD-L1 in HCC cells.•IFN-γ enhances PD-L1 expression via STAT1 signaling.•IL-1β enhances PD-L1 expression via the NF-κB and the p38 MAPK pathways.•IRF-1 and IFNGR also contribute to the synergistic effect of IFN-γ and IL-1β in HCC.