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Visualization of IL-22-expressing Lymphocytes Using Reporter Mice
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IL-23促进瘤发生率和生长
John L Langowski1, Xueqing Zhang, Lingling Wu
1Schering-Plough BioPharma, 901 California Avenue, Palo Alto, California 94304, USA.
Nature
|May 12, 2006
概括
介质素-23 (IL-23) 促进瘤炎症,并通过减少细胞毒性T细胞透来阻碍免疫监测. 消除IL-23可以增强抗瘤免疫力,并防止癌症的发展.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 炎症研究 炎症研究
背景情况:
- 慢性炎症与癌症发病率的增加有关.
- 与瘤相关的炎症与慢性炎症有共同的机制,包括免疫细胞透和血管生成.
- 由细胞毒性T细胞介导的免疫监测对于消除早期恶性病变至关重要.
研究的目的:
- 为了研究瘤相关炎症和免疫监测受损之间的分子联系.
- 确定介素-23 (IL-23) 在调节瘤微环境和免疫细胞透中的作用.
- 评估向IL-23在癌症预防和治疗中的治疗潜力.
主要方法:
- 在人类瘤中对IL-23和IL-12表达的分析.
- 研究IL-23对炎症反应,矩阵金属蛋白酶活性和血管生成的影响.
- 评估CD8 T细胞透的IL-23调节的反应.
- 在化学诱导和移植瘤的小鼠模型中利用基因删除和抗体介导的IL-23消除.
主要成果:
- 人类瘤中IL-23的表达升高,与其相对IL-12不同.
- IL-23促进了促炎反应,矩阵金属蛋白酶9 (MMP9) 的上调和血管生成.
- IL-23 抑制了细胞毒性 CD8 T 细胞透到瘤中的过程.
- 缺少或阻断IL-23可增强细胞毒性T细胞的透,并提供对化学诱导的癌症发生的保护.
- 在缺乏IL-23或缺乏IL-23受体的小鼠中,瘤生长受到限制.
结论:
- IL-23作为关键的分子调解剂,将促进瘤炎症与适应性免疫监测的失败联系起来.
- 向IL-23可以克服效应细胞透到瘤中的障碍,从而增强抗瘤免疫力.
- 调节IL-23代表了癌症免疫治疗的有希望的策略.
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