Expression of interleukins-23 and 27 leads to successful gene therapy of hepatocellular carcinoma

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• 作者：Peng Hu ; Huai-Dong Hu ; Min Chen ; Ming-Li Peng ; Li Tang ; Kai-Fu Tang ; Masanori Matsui ; Maria Laura Belladonna ; Takayuki Yoshimoto ; Da-Zhi Zhang ; Rong Xiang ; Hong Ren
• 关键词：Interleukin ; IL-23 ; IL-27 ; Immunotherapy ; Cytokine ; CD8⁺T cells ; IFN-γ
• 刊名：Molecular Immunology
• 出版年：2009
• 出版时间：May 2009
• 年：2009
• 卷：46
• 期：8-9
• 页码：1654-1662
• 全文大小：1103 K

文摘

IL-23 and IL-27 are two novel IL-12 cytokine family members who are quite similar to, but yet clearly distinct from IL-12 in their structures and T-cell stimulatory mechanisms. Here, we demonstrated that either IL-27 or IL-23 has potent antitumor activity in murine models of MM45T.Li hepatocellular carcinoma (HCC). These potent antitumor effects were induced primarily by CD8⁺T cells, secreting IFN-γ while CD4⁺T cells were also involved as a help of antitumor immunity. However, the antitumor response induced by IL-27 was observed from an early stage of tumor growth whereas that of IL-23 was only evident in the late stage of tumor cell proliferation. IL-23 could induce mice to develop a long-term systemic immunologic memory response against parental MM45T.Li tumors cells, an effect IL-27 was not able to accomplish. CTLs specific for MM45T.Li cells were significantly induced by IL-23, whereas antitumor efficacy mediated by IL-27 and IL-12 involved NK cells, which IL-23 failed to activate. Furthermore, we demonstrated that CD40 expression also plays an important role in the induction of antitumor activities by IL-27, IL-23 or IL-12. Together our data suggest that IL-27 and IL-23 may be two novel and attractive candidate agents to apply to cancer immunotherapy.