Interleukin (IL)-24 transforms the tumor microenvironment and induces anticancer immunity in a murine model of colon cancer
Interleukin (IL)-24 transforms the tumor microenvironment and induces anticancer immunity in a murine model of colon cancer
复制标题
白细胞介素 (IL)-24 可改变肿瘤微环境并在小鼠结肠癌模型中诱导抗癌免疫。
DOI：
10.1016/j.molimm.2016.05.010
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发表时间：
2016-07-01
影响因子：
3.6
通讯作者：
Ji, Yanhong
中科院分区：
文献类型：
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作者：
Ma, Yun-Feng;Ren, Yi;Ji, Yanhong
白细胞介素-24（IL-24）是一种新型肿瘤抑制因子，可介导外周血单核细胞诱导产生Th 1型细胞因子。先前已检查了IL-24的个体特性;然而，先前尚未针对结肠癌（中国最常诊断的癌症）评估其体内免疫学后果和抗肿瘤特性。因此，我们评估了IL-24是否可以在具有完整免疫能力的小鼠模型中抑制结肠癌的进展，并探索了IL-24对体内结肠癌进展的免疫学作用的潜在机制。在这些小鼠模型中，我们发现IL-24在体内促进CD 4（+）T细胞和CD 8（+）T细胞分泌干扰素γ，并增强CD 8（+）T细胞的细胞毒性。更重要的是，我们证明了IL-24改变了肿瘤微环境，增强了抗肿瘤作用，有利于肿瘤根除。此外，IL-24表达与人结直肠癌的临床分期呈负相关。因此，我们的研究确立了IL-24在促进抗肿瘤免疫应答中的作用，并支持开发针对结肠癌的新型细胞因子免疫疗法。(C)2016爱思唯尔有限公司版权所有。
Interleukin-24 (IL-24) is a novel tumor suppressor and can mediate the induction of Th1-type cytokines from peripheral blood mononuclear cells. The individual properties of IL-24 have been previously examined; however, its in vivo immunological consequences and antitumor properties have not been previously evaluated with respect to colon cancer, the most commonly diagnosed cancer in China. Thus, we evaluated whether IL-24 could inhibit the progression of colon cancer in murine models with intact immune competence and explored the mechanisms underlying the immunological effects of IL-24 on colon cancer progression in vivo. In these murine models, we found that IL-24 promoted CD4(+) T cells and CD8(+) T cells to secrete interferon gamma and enhanced the cytotoxicity of CD8(+) T cells in vivo. More importantly, we demonstrated that IL-24 transformed the tumor microenvironment and enhanced antitumor effects in favor of tumor eradication. Additionally, IL-24 expression correlated inversely with the clinical stage of human colorectal cancer. Thus, our study establishes a role of IL-24 in promoting antitumor immune responses and supports the development of a novel cytokine immunotherapy against colon cancer. (C) 2016 Elsevier Ltd. All rights reserved.