Membrane IL1α Inhibits the Development of Hepatocellular Carcinoma via Promoting T- and NK-cell Activation

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 alpha is one of the most important inflammatory cytokines involved in inflammation and tumor development. IL1 alpha 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 alpha in hepatocellular carcinoma tumorigenesis is still not clear. Here, we examined the functions of membrane IL1 alpha in murine hepatocellular carcinoma models. We found that membrane IL1 alpha potently inhibited hepatocellular carcinoma tumor growth. Further studies showed that membrane IL1 alpha promoted T-and natural killer (NK)-cell activation in vivo. IFN gamma production by CD8(+) T and NK cells was also increased as a result of membrane IL1 alpha expression. Moreover, the cytotoxicity of the CTL and NK cells was also enhanced by membrane IL1 alpha expression. Furthermore, in vitro studies demonstrated that membrane IL1 alpha 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 alpha. Our studies demonstrated that membrane IL1 alpha could promote antitumor immune responses through activation of T and NK cells. Thus, our findings provide new insights of IL1 alpha functions during hepatocellular carcinoma development. (C) 2016 AACR.