相关实验视频

Updated: Jul 4, 2025

A Protocol for Explant Cultures of IDH1-mutant Diffuse Low-grade Gliomas

A Protocol for Explant Cultures of IDH1-mutant Diffuse Low-grade Gliomas

Published on: May 9, 2025

ATRX和IDH1突变之间的相互作用控制了扩散性结质瘤中的先天免疫反应

Seethalakshmi Hariharan^1,2, Benjamin T Whitfield³, Christopher J Pirozzi^1,4

¹The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.

Nature communications

|January 25, 2024

概括

失去ATRX会使质瘤细胞产生先天性免疫反应,但IDH1^R132H突变掩盖了这一效应. 准先天性免疫力为星系细胞瘤提供了一个新的治疗策略.

科学领域:

神经瘤学神经瘤学
免疫学免疫学免疫学
癌症生物学癌症生物学

背景情况:

天生的免疫系统刺激是潜在的质瘤治疗方法.
在IDH突变天体细胞瘤中ATRX突变与免疫功能障碍有关.
遗传免疫中ATRX损失和IDH突变之间的相互作用尚不清楚.

研究的目的:

为了研究ATRX损失和IDH1^R132H突变对质瘤先天免疫的综合影响.
探索向天体细胞瘤天生的免疫力的治疗潜力.

主要方法:

生成的ATRX缺陷质瘤模型,具有或没有IDH1^R132H突变.
对基于dsRNA的先天性免疫激动症的评估敏感性.
在体内评估的致死性和T细胞透.
研究了IDH1^R132H对免疫基因表达的影响及其抑制的影响.

主要成果:

缺少ATRX的质瘤细胞对dSRNA激动体表现出敏感性,致命性受损,T细胞透率增加.
IDH1^R132H突变抑制了基线先天性免疫基因和细胞因子表达.
IDH1^R132H的遗传和药理抑制恢复了免疫基因表达.
IDH1^R132H没有阻碍ATRX缺陷驱动的dsRNA敏感性.
对于 dsRNA 识别,ATRX 损失使细胞变为原始细胞,这种 recognition 被 IDH1^R132H可逆地掩盖.

结论:

失去ATRX使星系细胞对基于dsRNA的免疫刺激敏感.
IDH1^R132H突变可逆地抑制了这种先天性免疫原始化.
天生的免疫力代表了天体细胞瘤的治疗脆弱性.

更多相关视频

Primary Orthotopic Glioma Xenografts Recapitulate Infiltrative Growth and Isocitrate Dehydrogenase I Mutation

Primary Orthotopic Glioma Xenografts Recapitulate Infiltrative Growth and Isocitrate Dehydrogenase I Mutation

Published on: January 14, 2014

Digital Spatial Profiling for Characterization of the Microenvironment in Adult-Type Diffusely Infiltrating Glioma

Digital Spatial Profiling for Characterization of the Microenvironment in Adult-Type Diffusely Infiltrating Glioma

Published on: September 13, 2022

相关概念视频

Intracellular Signaling Affects Focal Adhesions

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...

The Intrinsic Apoptotic Pathway

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...