Membrane IL1? inhibits the development of hepatocellular carcinoma via promoting T- and NK-cell activation

Abstract

Hepatocellular carcinoma is a worldwide health problem with limited treatment options and poor prognosis. Inflammation associated with liver injury and hepatocyte regeneration can lead to fibrosis, cirrhosis, and eventually, hepatocellular carcinoma. IL1? is one of the most important inflammatory cytokines involved in inflammation and tumor development. IL1? presents as multiple forms in vivo, including precursor, propiece, membrane, and secreted forms, and their functions have been thought to be different. The role of membrane IL1? in hepatocellular carcinoma tumorigenesis is still not clear. Here, we examined the functions of membrane IL1? in murine hepatocellular carcinoma models. We found that membrane IL1? potently inhibited hepatocellular carcinoma tumor growth. Further studies showed that membrane IL1? promoted T- and natural killer (NK)-cell activation in vivo. IFN? production by CD8+ T and NK cells was also increased as a result of membrane IL1? expression. Moreover, the cytotoxicity of the CTL and NK cells was also enhanced by membrane IL1? expression. Furthermore, in vitro studies demonstrated that membrane IL1? could directly activate T cells and NK cells in a cell contact-dependent manner. Conversely, depletion of both CD8+ T and NK cells suppressed the antitumor activity of membrane IL1?. Our studies demonstrated that membrane IL1? could promote antitumor immune responses through activation of T and NK cells. Thus, our findings provide new insights of IL1? functions during hepatocellular carcinoma development. ©2016 AACR.