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白细胞介素-12诱导CD8(+)细胞毒性T淋巴细胞对小鼠乳腺癌激活过程中的全基因组表达谱分析

Global gene expression profiling in interleukin-12-induced activation of CD8(+) cytotoxic T lymphocytes against mouse mammary Carcinoma.

作者信息

Cao Shanjin, Xiang Zhaoying, Ma Xiaojing

机构信息

Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York 10021, USA.

出版信息

Cell Mol Immunol. 2004 Oct;1(5):357-66.

Abstract

Interleukin-12 (IL-12) is a critical cytokine representing the link between the cellular and humoral branches of host immune defense apparatus. IL-12-induced cytotoxic lymphocyte (CTL) development is a central mechanism in immune responses against intracellular infectious agents as well as malignant growth. However, the molecular basis of tumor-specific CTL responses mediated by IL-12 remains poorly defined. In this study, we addressed this issue in a comprehensive manner to probe into IL-12-induced anti-tumor responses by global gene expression profiling of mRNA expression in CD8(+) T cells in a transplantable syngeneic mouse mammary carcinoma model treated or not with recombinant IL-12. A strong tumor regression was induced by the IL-12 treatment. An introspection of differential gene expression at an early stage of the IL-12-initiated CTL activation reveals interesting genes and molecular pathways that may account for the marked tumor regression, and is likely to provide a rich source of potential targets for further research and development of effective therapeutic modalities.

摘要

白细胞介素-12(IL-12)是一种关键的细胞因子,代表宿主免疫防御系统细胞和体液分支之间的联系。IL-12诱导的细胞毒性淋巴细胞(CTL)发育是针对细胞内感染因子以及恶性生长的免疫反应中的核心机制。然而,IL-12介导的肿瘤特异性CTL反应的分子基础仍不清楚。在本研究中,我们通过对可移植同基因小鼠乳腺癌模型中经重组IL-12处理或未处理的CD8(+) T细胞中的mRNA表达进行全基因表达谱分析,以全面探讨IL-12诱导的抗肿瘤反应,从而解决了这个问题。IL-12处理诱导了强烈的肿瘤消退。对IL-12启动的CTL激活早期阶段的差异基因表达进行的深入分析揭示了可能导致显著肿瘤消退的有趣基因和分子途径,并可能为有效治疗方法的进一步研究和开发提供丰富的潜在靶点来源。

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