科尔迪塞普斯辛尼西斯的生物活性脂通过SphK1-介导的Cer/S1P轴调节瘤免疫力
Qi-Xuan Kuang1, Chen-Yi Yan2, Chao-Yu Wang1
1TCM Prevention and Treatment of Metabolic and Chronic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China.
Phytotherapy research : PTR
|January 28, 2026
概括
来自Cordyceps sinensis的生物活性脂通过向SphK1通路来增强抗PD-1癌症治疗. 这种天然化合物组合增强T细胞免疫力,并克服肺癌模型中的治疗耐药性.
科学领域:
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
- 自然产品 化学 化学
背景情况:
- 科尔迪塞普斯·辛内西斯生物活性脂 (SPLs) 显示出抗瘤潜力,但其机制尚不清楚.
- 了解SPL与抗PD-1疗法的协同作用对于克服癌症治疗耐药性至关重要.
研究的目的:
- 确定来自C. sinensis的活跃的SPL.
- 研究它们与抗PD-1疗法的协同效应.
- 阐明涉及氨酸激酶1 (SphK1) 的潜在机制.
主要方法:
- 在C. sinensis.的SPL中进行UPLC-MS/MS引导的净化.
- 在体内 (LLC小鼠模型) 和体内评估抗瘤疗效和与αPD-1的免疫调节协同作用.
- 使用生物化学试验,SPR,分子对接和模拟来探索SphK1机制.
主要成果:
- 与αPD-1结合的SPL增强了抗瘤免疫力,增加了CD8+T细胞透率并减少了PD-L1表达.
- SPL的目标是SphK1-介导的胺/胺-1-酸盐 (Cer/S1P) 轴,促进抗瘤免疫力.
- 鉴定出一种新型的胺,即cordysinamide A,它直接与SphK1结合,抑制S1P的产生,从而增加IL-2和IFN-γ.
结论:
- 来自C. sinensis的SPL通过调节SphK1-介导的Cer/S1P平衡来克服αPD-1抵抗.
- 这种基于天然产品的策略可以改变免疫抑制瘤代谢,为非小细胞肺癌治疗提供潜力.
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