由棕酸触发的B7H3棕化促进了免疫逃生
Zejun Rao1, Changsheng Huang1, Qi Wu1
1GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Nature communications
|January 19, 2026
概括
微卫星稳定的结直肠癌需要新的治疗方法. 科学家们发现,阻断B7H3棕化会提高T细胞的反应,提供一种新的免疫治疗点.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 具有微卫星稳定性 (MSS) 的结肠直肠癌 (CRC) 对免疫检查点封锁的反应有限.
- B7H3 (CD276) 是一种在许多瘤中过度表达的免疫检查点蛋白,但其稳定机制尚不清楚.
- 了解B7H3调节对于开发新型CRC免疫疗法至关重要.
研究的目的:
- 研究癌症中维持高B7H3蛋白水平的机制.
- 探索B7H3棕化作为MSS CRC.的潜在治疗标.
- 评估加强对结直肠癌抗瘤免疫力的策略.
主要方法:
- 研究了棕酸 (PA) 和ZDHHC24在B7H3棕化中的作用.
- 评估了B7H3棕化对其与顺序素1 (SQSTM1/p62) 的相互作用以及随后的降解的影响.
- 在大肠炎相关结肠直肠癌 (CAC) 鼠标模型中利用了基因修饰 (C496A突变,Zdhhc24删除).
- 开发并测试了一种针对ZDHHC24-B7H3相互作用的细胞透性.
- 评估了与抗编程细胞死亡蛋白1 (PD-1) 治疗的协同作用.
主要成果:
- 棕酸 (PA) 通过ZDHHC24在氨酸496促进B7H3棕化,稳定了B7H3蛋白.
- 这种棕化会阻止B7H3与SQSTM1结合,从而抑制自性降解.
- 稳定B7H3抑制CD8+T细胞的抗瘤活性.
- 破坏B7H3棕化 (通过C496A突变或Zdhhc24删除) 在CAC模型中增强了CD8+ T细胞的反应.
- 一种阻断ZDHHC24-B7H3相互作用的可以增强抗瘤免疫力,并与PD-1阻断产生协同作用.
结论:
- 通过ZDHHC24进行B7H3棕化是B7H3稳定的一个关键机制,抑制了结直肠癌中的抗瘤免疫力.
- 针对这种代谢免疫节点,特别是B7H3棕化,是增强结直肠癌免疫疗法的有希望的策略.
- 开发的提供了一种潜在的治疗方法,以克服对PD-1封锁等当前免疫疗法的耐药性.
相关概念视频
Escape Velocity
8.3K
The escape velocity of an object is defined as the minimum initial velocity that it requires to escape the surface of another object to which it is gravitationally bound and never to return. For example, what would be the minimum velocity at which a satellite should be launched from the Earth's surface such that it just escapes the Earth's gravitational field?
To calculate the escape velocity, it is assumed that no energy is lost to any frictional forces. In practice, a satellite...
To calculate the escape velocity, it is assumed that no energy is lost to any frictional forces. In practice, a satellite...
8.3K
Escape Velocities of Gases
1.3K
To escape the Earth's gravity, an object near the top of the atmosphere at an altitude of 100 km must travel away from Earth at 11.1 km/s. This speed is called the escape velocity. The temperature at which gas molecules attain the rms speed, which is equal to the escape velocity, can be estimated by using the equation for the average kinetic energy of the gas molecules. According to the kinetic theory of gas, the average kinetic energy of the gas molecules is proportional to its...
1.3K
What is the Immune System?
127.0K
Overview
127.0K
The Eukaryotic Promoter Region
18.7K
The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences. The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
18.7K
The Eukaryotic Promoter Region
3.8K
3.8K
Humoral Immune Responses
83.4K
Overview
83.4K


