CMTM6通过调节CD58和PD-L1的蛋白质表达来塑造抗瘤T细胞的反应
Beiping Miao1, Zhaoqing Hu2, Riccardo Mezzadra3
1German Cancer Research Center (DKFZ) Heidelberg, Division Immune Regulation in Cancer, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Cancer cell
|September 8, 2023
概括
癌细胞通过免疫检查点逃避免疫破坏. 这项研究揭示了CMTM6调节CD58,这是一个关键的辅助刺激配体,影响T细胞相互作用和免疫治疗反应.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 分子细胞生物学 分子细胞生物学
背景情况:
- 癌细胞通过调节免疫检查点分子来逃避免疫监测.
- 目前针对PD-L1等抑制检查点的免疫疗法可能由于不够的共刺激信号而无效.
- CD58是一种关键的辅助刺激性连接体,对抗瘤免疫力至关重要,但其表达调节的理解不足.
研究的目的:
- 阐明控制CD58表达的调控机制.
- 为了确定免疫检查点连接体的新型调节剂.
- 了解瘤微环境中的共刺激和共抑制信号之间的相互作用.
主要方法:
- 系统选方法用于识别CD58.8的调节者.
- 同免疫沉试验用于研究蛋白质与蛋白质相互作用.
- 功能性测试评估T细胞和瘤细胞相互作用以及对PD-L1阻塞的反应.
主要成果:
- CMTM6被确定为CD58表达的积极调节者.
- CMTM6直接与CD58和PD-L1相互作用,稳定它们的表达.
- 瘤细胞表达CMTM6和CD58影响T细胞参与和PD-L1-PD-1阻断的有效性.
结论:
- CMTM6在调节CD58表达方面发挥着至关重要的作用.
- CMTM6作为刺激性 (CD58) 和抑制性 (PD-L1) 免疫检查点的共享调节器.
- 瘤内在的CMTM6和CD58表达是抗瘤免疫反应和免疫治疗结果的重要决定因素.
相关概念视频
Inhibition of Cdk Activity
4.8K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
Abnormal Proliferation
4.6K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
T Cell Activation and Clonal Selection
801
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
801
The Tumor Microenvironment
6.7K
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...
6.7K
Tumor Immunotherapy
554
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.
554
Cytotoxic T Cells-mediated Immune Response
959
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
959


