针对结合粘附分子样蛋白+ CD8+ T细胞的向激活增强了肝细胞癌的免疫疗法
Huan Chen1, Zhaofeng Xiao1, Zhengyang Lu1
1The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China.
概括
激活结合粘附分子样蛋白 (JAML) 增强细胞毒性T淋巴细胞 (CTL) 对肝细胞癌 (HCC) 的反应. 这种方法对治疗先进的HCC具有前景,独立于现有的免疫疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 细胞毒性T淋巴细胞 (CTLs) 对于肝细胞癌 (HCC) 治疗至关重要.
- 已知结合粘附分子样蛋白 (JAML) 能促进CD8+T细胞的抗瘤活性.
- 了解JAML在HCC中的作用对于开发新疗法至关重要.
研究的目的:
- 为了研究JAML表达的CD8+ T细胞在HCC中的功能.
- 探索HCC患者中CD4+ T细胞分化和JAML+ CD8+ T细胞之间的相关性.
- 评估针对JAML在HCC中的治疗潜力.
主要方法:
- 利用了飞行时间质量细胞计和HCC.的正位体小鼠模型.
- 通过流式细胞计量评估了瘤透的CD8+T细胞中的CD4+T细胞分化和JAML表达.
- 进行了抗JAML抗体治疗,并进行了RNA测序以确定机制.
主要成果:
- 免疫疗法增加了CD8+ T细胞的透,并诱导了组织蛋白修饰,包括CD4+ T细胞中的H3K18乳酸化.
- 乳酸脱酶A (LDHA) + CD4+ T细胞与免疫疗法响应者中的JAML+ CD8+ T细胞正相关.
- 抗JAML抗体治疗减少了瘤体积,并改善了小鼠的存活率,独立于抗PD-L1治疗.
结论:
- 激活JAML可增强HCC中CTL反应,提供一种新的治疗策略.
- 针对JAML是一个有前途的途径,用于治疗先进的HCC.
- JAML的机制涉及通过氧化酸化途径增强CTL反应.
相关概念视频
01:17Intracellular Signaling Affects Focal Adhesions
2.5K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.5K
01:26Tension Response at Adherens Junctions
2.6K
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
2.6K
01:24Adherens Junctions
4.6K
Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types – adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
Adherens Junctions are Dynamic
Adherens Junctions are Dynamic
4.6K
01:31Immunoglobulin-like Cell Adhesion Molecules
3.2K
Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
3.2K
01:03Anchoring Junctions
3.5K
Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...
3.5K
01:15Activation of Integrins
3.2K
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
3.2K