Expression of interleukins-23 and 27 leads to successful gene therapy of hepatocellular carcinoma
Expression of interleukins-23 and 27 leads to successful gene therapy of hepatocellular carcinoma
复制标题
白细胞介素23和27的表达导致肝细胞癌基因治疗成功
DOI：
10.1016/j.molimm.2009.02.025
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发表时间：
2009-05-01
影响因子：
3.6
通讯作者：
Rena, Hong
中科院分区：
文献类型：
--
作者：
Hu, Peng;Hu, Huai-Dong;Rena, Hong
IL-23和IL-27是两种新的IL-12细胞因子家族成员，它们在结构和T细胞刺激机制上与IL-12非常相似，但又明显不同。在此，我们证明了IL-27或IL-23在MM45T.Li肝细胞癌（HCC）小鼠模型中具有有效的抗肿瘤活性。这些强效抗肿瘤作用主要由分泌IFN-γ的CD 8（+）T细胞诱导，而CD 4（+）T细胞也参与了抗肿瘤免疫的帮助。然而，IL-27诱导的抗肿瘤反应从肿瘤生长的早期阶段观察到，而IL-23仅在肿瘤细胞增殖的晚期阶段明显。IL-23可诱导小鼠产生针对亲代MM45T.Li肿瘤细胞的长期全身免疫记忆应答，这是IL-27不能实现的效果。IL-23显著诱导了对MM45T.Li细胞特异性的CTL，而IL-27和IL-12介导的抗肿瘤功效涉及IL-23未能激活的NK细胞。此外，我们证明了CD 40表达在IL-27、IL-23或IL-12诱导抗肿瘤活性中也起重要作用。总之，我们的数据表明，IL-27和IL-23可能是两种新的和有吸引力的候选药物，适用于癌症免疫治疗。(C)2009爱思唯尔有限公司保留所有权利。
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-gamma 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. (C) 2009 Elsevier Ltd. All rights reserved.