来自瘤的可溶性MIC配体损害NKG2D和T细胞激活的表达
Veronika Groh1, Jennifer Wu, Cassian Yee
1Fred Hutchinson Cancer Research Center, Clinical Research Division, 1100 Fairview Avenue North, Seattle, Washington 98109, USA. vgroh@fhcrc.org
Nature
|October 18, 2002
概括
瘤细胞释放可溶性MICA,从而降解T细胞上的NKG2D受体. 这会损害T细胞的反应,使瘤能够逃避免疫检测,并可能增加感染易感性.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 细胞信号传输 细胞信号传输
背景情况:
- 瘤配体的NKG2D受体参与可以刺激淋巴细胞对瘤排斥的反应.
- NKG2D在自然杀手 (NK) 细胞, gamma delta T 细胞和 CD8alphabeta T 细胞上表达.
- 主体组织相容性复合物I类链相关分子 (MIC) A和B是NKG2D的压力诱导的配体,通常表达在上皮瘤中.
研究的目的:
- 研究MIC参与对NKG2D受体表达和功能的影响.
- 确定瘤可能逃避免疫监测的机制.
- 了解可溶性MIC对癌症患者T细胞响应性的影响.
主要方法:
- 研究了MIC和NKG2D之间的相互作用.
- 分析了来自癌症患者的T细胞上的NKG2D表达.
- 评估了溶性MICA在NKG2D下调和T细胞功能的作用.
主要成果:
- MIC与NKG2D的结合会诱导内细胞分裂和NKG2D受体的降解.
- 在癌症患者的T细胞上,NKG2D的表达显著减少.
- 循环中的溶性MICA与NKG2D下调和瘤抗原特异性T细胞的响应能力受损相关.
结论:
- 瘤衍生的可溶性MICA导致全身NKG2D缺乏,损害T细胞介导的抗瘤免疫力.
- 这种NKG2D下调代表了瘤免疫逃避的机制.
- 这些发现表明,由于T细胞功能受损,宿主对感染的抵抗力受到损害.
更多相关视频
06:55Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells
Published on: February 22, 2020
19.6K
07:44Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports
Published on: November 28, 2019
8.2K
相关概念视频
01:15Receptor Downregulation in MVBs
2.9K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.9K
02:17The Tumor Microenvironment
8.0K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
8.0K
01:27Tumor Immunotherapy
2.1K
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
2.1K
02:38Mitogens and the Cell Cycle
8.2K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
8.2K