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白细胞介素(IL)-24可改变肿瘤微环境,并在结肠癌小鼠模型中诱导抗癌免疫。

Interleukin (IL)-24 transforms the tumor microenvironment and induces anticancer immunity in a murine model of colon cancer.

作者信息

Ma Yun-Feng, Ren Yi, Wu Cai-Jun, Zhao Xiao-Hui, Xu Hua, Wu Da-Zhou, Xu Jiru, Zhang Xiao-Lian, Ji Yanhong

机构信息

Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, PR China, PR China.

Department of Breast and Thyroid Surgery, Huai'an First People Hospital, Huai'an, Jiangsu 223300, PR China.

出版信息

Mol Immunol. 2016 Jul;75:11-20. doi: 10.1016/j.molimm.2016.05.010. Epub 2016 May 19.

Abstract

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.

摘要

白细胞介素-24(IL-24)是一种新型肿瘤抑制因子,可介导外周血单个核细胞产生Th1型细胞因子。此前已对IL-24的个体特性进行过研究;然而,其在体内的免疫学后果和抗肿瘤特性,针对中国最常见的诊断癌症——结肠癌,此前尚未进行评估。因此,我们评估了IL-24是否能在具有完整免疫能力的小鼠模型中抑制结肠癌的进展,并探讨了IL-24对体内结肠癌进展产生免疫效应的潜在机制。在这些小鼠模型中,我们发现IL-24可促进CD4(+) T细胞和CD8(+) T细胞分泌干扰素γ,并增强体内CD8(+) T细胞的细胞毒性。更重要的是,我们证明IL-24可改变肿瘤微环境并增强抗肿瘤效应,有利于根除肿瘤。此外,IL-24的表达与人类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在促进抗肿瘤免疫反应中的作用,并支持开发一种针对结肠癌的新型细胞因子免疫疗法。

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