人类烯碳化合物受体的内源性促进瘤的配体
Christiane A Opitz1, Ulrike M Litzenburger, Felix Sahm
1Department of Neurooncology, Neurology Clinic and National Center for Tumor Diseases, University Hospital of Heidelberg, 69120 Heidelberg, Germany.
Nature
|October 7, 2011
概括
研究人员确定了氨酸 (Kyn),一个氨酸 (Trp) 代谢物,作为氨酸碳化合物受体 (AHR) 的内源性配体. 这种TDO-AHR通路促进瘤生长和免疫抑制,影响癌症的进展.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 分子生物学分子生物学
背景情况:
- 基碳化合物受体 (AHR) 被环境毒素激活,并参与细胞过程.
- 在生理条件下AHR的内源性连接体仍然未确定.
研究的目的:
- 为了确定人类AHR的内源性配体.
- 研究TDO-AHR途径在癌症生物学和免疫反应中的作用.
主要方法:
- 鉴定金氨酸 (Kyn) 是一种内源的AHR配体.
- 在瘤细胞中分析二二氧化酶 (TDO) 活性.
- 评估TDO-AHR途径在瘤免疫抑制,生存和运动性中的作用.
- TDO-AHR通路活性与人类脑瘤进展和存活率的相关性.
主要成果:
- 丁氨酸 (Kyn) 是一种底 (Trp) 催化剂,被确定为人类AHR的新型内源性联结体.
- 人类瘤细胞通过二二氧化酶 (TDO) 构成性地产生Kyn.
- 来自TDO的Kyn抑制了抗瘤免疫反应,并通过AHR促进了瘤细胞的存活和运动.
- 在人类大脑瘤中,TDO-AHR通路是活跃的,与恶性进展和低生存率相关.
结论:
- kynurenine (Kyn) 是一种以前未被识别的内源性联体,可以激活AHR.
- TDO-AHR途径代表了免疫抑制和瘤进展的新机制.
- 这一途径对癌症和免疫生物学有重大影响,提供了潜在的治疗点.
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