CD58-CD2轴通过CMTM6与PD-L1共同调节,形成抗瘤免疫力
Patricia Ho1, Johannes C Melms1, Meri Rogava1
1Department of Medicine, Division of Hematology and Oncology, Columbia University, New York, NY 10032, USA; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA.
Cancer cell
|June 16, 2023
概括
癌细胞使用CD58和PD-L1.1平衡免疫信号. 完整的CD58促进抗瘤免疫力,并预测治疗反应,而缺陷导致免疫逃避.
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:
- 癌症免疫规避依赖于平衡免疫抑制和刺激信号.
- CD58-CD2轴在抗瘤免疫和治疗反应中发挥作用.
研究的目的:
- 研究癌细胞内在CD58表达在抗瘤免疫中的作用.
- 确定调节CD58稳定性的分子机制及其与PD-L1.1的相互作用.
主要方法:
- 来自患者的共同培养.
- 人性化的小鼠模型
- 单细胞RNA测序的测序方法
- 在CRISPR-Cas9屏幕上
- 蛋白质组学是指蛋白质组学.
主要成果:
- 完整的癌细胞CD58表达和CD2结合对于抗瘤免疫和预测治疗反应至关重要.
- 在CD58-CD2轴的缺陷损害T细胞激活,透和增殖,同时增加PD-L1.1.
- CMTM6被确定为CD58稳定性和CD58损失后PD-L1上调的关键调节器.
- 对CMTM6结合的竞争影响CD58和PD-L1内体循环与降解.
结论:
- 一个涉及CD58和CD2的关键轴调节癌症免疫和免疫逃避.
- CMTM6调解免疫刺激 (CD58) 和抑制 (PD-L1) 信号之间的平衡.
- 了解这一轴为癌症免疫逃避和潜在的治疗策略提供了分子基础.
相关概念视频
T Cell Activation and Clonal Selection
837
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...
837
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
575
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.
575


