IL-17B Inhibits Hepatocellular Carcinoma Cell Proliferation

Abstract IL-17RB is a cytokine receptor that binds interleukin (IL)-17B and IL-17E. While analyzing IL-17RB expression in various cancer cell lines, we found that this receptor is highly expressed at both the mRNA and protein levels in hepatocellular carcinoma (HCC) cells. This finding prompted us to investigate the effects of its ligand, IL-17B, on the proliferation of these cells. Our results demonstrate that IL-17B inhibits the proliferation of HCC cells through an AKT-dependent, but NF-κB-independent, mechanism. Additionally, IL-17B affected colony formation in these cells. Interestingly, these effects were not observed in melanoma cells, which express low levels of IL-17RB. Our results may represent a promising new approach for treating HCC – a disease for which immunological therapies have recently gained significant attention – especially considering that HCC patients experience progressive liver dysfunction and that the IL-17B–IL-17RB signaling pathway plays a role in liver regeneration.