CBX2通过非正规核心抑制器复合体抑制干扰素信号,以减少瘤免疫性
Yanxun Lin1, Huan Jin1, Yong She1
1State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510050, China.
概括
染色盒2 (CBX2) 通过抑制通过非正规复合体进行干扰素信号传递来抑制抗瘤免疫力. 抑制CBX2可以提高癌症免疫疗法的疗效.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 分子生物学分子生物学
背景情况:
- 染色盒2 (CBX2) 是参与癌症发展的多镇压复合体 (PRC) 的组成部分.
- CBX2在调节瘤免疫性和免疫逃避中的作用尚不清楚.
研究的目的:
- 研究CBX2在瘤免疫中的功能及其作为治疗点的潜力.
- 阐明CBX2影响瘤免疫微环境的分子机制.
主要方法:
- 利用小鼠同源性瘤模型来评估CBX2切除对瘤生长和免疫反应的影响.
- 进行了转录程序分析和质谱测量,以确定CBX2相互作用蛋白和调节通路.
- 研究了CBX2与RACK1和HDAC1的相互作用及其对H3K27ac修饰的影响.
主要成果:
- CBX2除抑制了瘤生长,激活了瘤免疫微环境,并增强了抗PD1和采用T细胞治疗的疗效.
- 发现CBX2可以抑制干扰素信号,而不依赖于其规范PRC功能.
- CBX2直接与RACK1相互作用,并招募HDAC1来减弱H3K27ac在干扰素刺激的基因促进器上,抑制干扰素信号传递.
结论:
- CBX2抑制瘤免疫性,并通过非正规的CBX2-RACK1-HDAC1核心抑制复合体促进免疫逃避.
- 高CBX2表达与免疫抑制瘤微环境和人类癌症免疫治疗效率降低相关.
- CBX2-RACK1-HDAC1复合体代表了癌症免疫治疗的潜在治疗标和生物标志物.
相关概念视频
Inhibition of Cdk Activity
4.6K
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...
4.6K
NF-κB-dependent Signaling Pathway
7.2K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.2K
X-Inactivation
38.0K
The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.
38.0K
Cytotoxic T Cells-mediated Immune Response
835
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...
835
Cancer-Critical Genes II: Tumor Suppressor Genes
7.3K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
7.3K
Eukaryotic Transcription Inhibitors
9.8K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
9.8K


