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STING是一种细胞内在的代谢检查点,通过准HK2来限制有氧糖解
Liting Zhang1,2,3,4, Congqing Jiang5, Yunhong Zhong1,2
1The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, State Key Laboratory of Virology, Medical Research Institute, Wuhan University, Wuhan, China.
Nature cell biology
|July 13, 2023
概括
STING通过抑制hexokinase II (HK2) 来限制瘤有氧糖解,这与其免疫作用无关. 这种代谢检查点功能促进抗瘤免疫力,提供新的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢途径 代谢途径
- 癌症生物学 癌症生物学
背景情况:
- 反瘤免疫的逃避是癌症的一个关键特征.
- 干扰基因刺激器 (STING) 是一种与生俱来的免疫适应器,对抗瘤免疫至关重要,在恶性瘤中经常被沉默.
- 通过STING抑制瘤的细胞内在机制尚未完全理解.
研究的目的:
- 研究STING在限制瘤生长中的细胞内在作用.
- 阐明STING的瘤抑制功能背后的分子机制,超出其已知的免疫作用.
- 探索STING,有氧糖解和抗瘤免疫之间的联系.
主要方法:
- 研究了STING对癌细胞中有氧糖解的影响.
- 使用生物化学测试来确定STING与hexokinase II (HK2) 的相互作用.
- 评估了STING介导的HK2抑制对瘤生长和体内抗瘤免疫力的影响.
- 在人类结直肠癌样本中,与乳酸水平和免疫标记物相关的STING表达.
主要成果:
- STING限制有氧糖解,独立于其正规的先天免疫信号通路.
- STING直接向并抑制了六基酶II (HK2) 的酶活性.
- 通过STING抑制HK2抑制瘤有氧糖解并增强体内抗瘤免疫力.
- 人类结直肠癌样本显示,STING表达,乳酸生产和抗瘤免疫力之间存在逆相关性.
结论:
- STING作为细胞内在的代谢检查点,限制有氧糖解以促进抗瘤免疫力.
- STING抑制HK2和有氧糖解的能力是抑制瘤的新机制.
- 这些发现凸显了STING作为增强抗瘤免疫疗法的潜在治疗点.
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