2016年3月，我所刘海燕教授课题组在《Cancer Research》上发表题为“Membrane IL1a Inhibits the Development of Hepatocellular Carcinoma via Promoting T- and NK-cell Activation”，研究发现膜型IL-1α可以通过活化T细胞和NK细胞来发挥抗肿瘤效应。这为IL-1α肿瘤免疫提供了新的理论基础，这也有可能使其成为肿瘤免疫治疗的新靶点。

IL-1α属于双功能细胞因子，它是一个非常重要的炎性因子，参与炎症和肿瘤的发展。IL-1α在体内存在多种形式，包括前体、propiece、膜型和分泌型，不同的形式具有不同的功能。

刘海燕教授课题组成功构建了表达膜型IL-1α的hepa1-6稳转细胞系。体外实验中，膜型的IL-1α会促进肿瘤细胞自身的增殖。而在体内实验中，三个肝癌模型中的膜型IL-1α均能有效抑制肝癌的发生发展。进一步的研究表明膜型IL-1α会以细胞接触的方式促进T细胞的活化。膜型IL-1α增加了肿瘤微环境中的NK、DC和巨噬细胞。此外膜型IL-1α还能促进CD8⁺T 和NK细胞产生IFN-γ，并能提高CTL的杀伤活性。

原文摘要：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. IL1a is one of the most important inflammatory cytokines involved in inflammation and tumor development. IL1a 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 IL1a in hepatocellular carcinoma tumorigenesis is still not clear. Here, we examined the functions of membrane IL1a in murine hepatocellular carcinoma models. We found that membrane IL1a potently inhibited hepatocellular carcinoma tumor growth. Further studies showed that membrane IL1a promoted T- and natural killer (NK)–cell activation in vivo. IFN-γ production by CD8t T and NK cells was also increased as a result of membrane IL1a expression. Moreover, the cytotoxicity of the CTL and NK cells was also enhanced by membrane IL1a expression. Furthermore, in vitro studies demonstrated that membrane IL1a could directly activate T cells and NK cells in a cell contact–dependent manner. Conversely, depletion of both CD8t T and NK cells suppressed the antitumor activity of membrane IL1a. Our studies demonstrated that membrane IL1a could promote antitumor immune responses through activation of T and NK cells. Thus, our findings provide new insights of IL1a functions during hepatocellular carcinoma development.