DEAD‐box helicase 1 inhibited CD8+ T cell antitumor activity by inducing PD‐L1 expression in hepatocellular carcinoma

Abstract

AbstractHepatocellular carcinoma (HCC) does not respond well to current treatments, even immune checkpoint inhibitors. PD‐L1 (programmed cell death ligand 1 or CD274 molecule)‐mediated immune escape of tumor cells may be a key factor affecting the efficacy of immune checkpoint inhibitor (ICI) therapy. However, the regulatory mechanisms of PD‐L1 expression and immune escape require further exploration. Here, we observed that DDX1 (DEAD‐box helicase 1) was overexpressed in HCC tissues and associated with poor prognosis in patients with HCC. Additionally, DDX1 expression correlated negatively with CD8+ T cell frequency. DDX1 overexpression significantly increased interferon gamma (IFN‐γ)‐mediated PD‐L1 expression in HCC cell lines. DDX1 overexpression decreased IFN‐γ and granzyme B production in CD8+ T cells and inhibited CD8+ T cell cytotoxic function in vitro and in vivo. In conclusion, DDX1 plays an essential role in developing the immune escape microenvironment, rendering it a potential predictor of ICI therapy efficacy in HCC.