相关实验视频

Updated: May 23, 2025

Generation of Human Chimeric Antigen Receptor Regulatory T Cells

Generation of Human Chimeric Antigen Receptor Regulatory T Cells

Published on: January 3, 2025

一个CARMIL2功能增益突变足以触发大多数CD28辅助刺激功能 in vivo

Fanghui Zhang^1,2, Javier Celis-Gutierrez¹, Lichen Zhang²

¹Centre d'Immunologie de Marseille-Luminy (CIML), Aix Marseille Université, Institut national de la santé et de la recherche médicale (INSERM), Centre national de la recherche scientifique (CNRS) , Marseille, France.

The Journal of experimental medicine

|May 22, 2025

概括

研究人员发现,CARMIL2-CARD11信号绕过了CD28对T细胞激活的依赖. 这一发现使强有力的抗瘤反应成为可能,即使CD28缺席或受到免疫检查点的抑制.

科学领域:

免疫学免疫学免疫学
分子生物学分子生物学
癌症研究癌症研究

背景情况:

原始T细胞的激活严重依赖于T细胞受体 (TCR) 和CD28协同刺激信号.
CARMIL2蛋白将CD28与CARD11适配器连接起来,从而促进CD28依赖的NF-κB激活.
卡米尔2的突变与人类T细胞恶性瘤有关.

研究的目的:

研究CARMIL2在T细胞激活中的作用.
开发一种模仿CARMIL2.2中人类T细胞恶性突变的小鼠模型.
探索CARMIL2-CARD11信号传导在克服CD28对抗瘤免疫的依赖性方面的潜力.

主要方法:

产生Carmil2QE突变小鼠,模仿人类T细胞恶性突变.
在野生型和突变T细胞中分析CARMIL2-CARD11复合体的形成.
在CD28缺乏和Carmil2QE突变小鼠中评估T细胞功能.
在没有CD28连接体和免疫检查点抑制剂的情况下,对瘤特异性T细胞反应的评估.

主要成果:

卡米尔2QE突变小鼠表现出预先形成的CARMIL2QE-CARD11复合体,在CD28接触时类似于野生类型细胞.
这些预先形成的复合体以CD28独立的方式诱导CD28类功能,即使在CD28缺乏的小鼠中也是如此.
表达Carmil2QE的瘤特异性T细胞绕过了对CD28参与的需要.
卡米尔2QE表达的T细胞逃避PD-1和CTLA-4的抑制,它们是关键的免疫检查点抑制剂.

结论:

在CD28介导的T细胞激活中,CARMIL2-CARD11信号传递起着核心作用.
利用CARMIL2-CARD11信号可以诱导强大的T细胞反应,独立于CD28.
这一策略为增强抗瘤免疫力提供了一个有希望的方法,克服对免疫检查点抑制剂的耐药性.

更多相关视频

Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses

Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses

Published on: May 6, 2019

In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function

In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function

Published on: February 27, 2019

相关概念视频

T Cell Activation and Clonal Selection

T Cell Activation and Clonal Selection

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...

Calmodulin-dependent Signaling

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...