在急性淋巴细胞白血病中,HVEM通过抑制CD8+T细胞功能来促进瘤免疫逃逸
Yujia Liu1,2, Lixiang Wang3,4, Yiyi Li2
1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
Cellular oncology (Dordrecht, Netherlands)
|May 29, 2024
概括
向疹病毒进入媒介 (HVEM) 显示出治疗急性淋巴细胞白血病 (ALL) 的希望. 废除HVEM表达抑制瘤生长并增强抗瘤免疫力,为ALL提供了一种新的治疗策略.
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:
- 白血病,特别是急性淋巴细胞白血病 (ALL),在全球范围内构成重大死亡风险.
- 目前针对ALL的治疗方法经常面临挑战,有效性有限,疾病复发.
研究的目的:
- 调查疹病毒进入媒介 (HVEM,TNFRSF14) 瘤表达的向潜力,作为急性淋巴细胞白血病 (ALL) 的治疗策略.
- 探索HVEM在ALL进展和复发中的作用,旨在确定新的治疗方法.
主要方法:
- 分析公共数据库,以将HVEM表达与白血病临床数据相关联.
- 使用CRISPR-Cas9.9生成HVEM淘汰赛 (KO) 鼠类T细胞淋巴细胞白血病细胞系 (EL4) 的基因.
- 建立用于体内研究的同源性皮下瘤模型.
- 使用免疫组织化学 (IHC),RNA-seq和流动细胞测量来分析瘤免疫微环境 (TIME) 和排水淋巴结 (dLNs).
- 在体内免疫子集枯竭和体内T细胞功能测试以调查免疫功能.
- 构建HVEM突变EL4细胞系,以确定负责免疫逃逸的功能域.
主要成果:
- 在ALL和急性髓性白血病 (AML) 患者中,HVEM的表达很高,与患者预后负相关.
- 在EL4细胞中HVEM的遗传删除显著抑制了瘤进展,并延长了瘤携带小鼠的存活时间.
- 在体内和体外,HVEM通过其CRD1域抑制抗瘤CD8+T细胞功能.
- 确定了一种组合疗法,可以完全根除所有瘤,并诱导保护性免疫记忆.
结论:
- 通过免疫抑制,HVEM在促进ALL进展方面发挥着至关重要的作用.
- 对于复发ALL的临床治疗来说,HVEM是一个有前途的治疗标.
- 向HVEM提供了一种潜在的策略,以提高治疗效率并防止ALL的复发.
更多相关视频
相关概念视频
Cytotoxic T Cells-mediated Immune Response
892
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...
892
T Cell Types and Functions
1.0K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.0K
Tumor Immunotherapy
515
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.
515
T Cell Activation and Clonal Selection
706
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...
706
Cells of the Innate Immune Response
1.6K
The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
1.6K


