检查点FLRT3-UNC5B通路抑制了基于T细胞的癌症免疫疗法
Kushal Prajapati1, Chuan Yan2,3, Qiqi Yang2,3
1NextCure Inc., Beltsville, MD 20705, USA.
Science advances
|March 1, 2024
概括
癌细胞使用轴突引导通路来逃避T细胞免疫力. 用抗体准富含纤维龙菌素白的跨膜蛋白3 (FLRT3) 可以恢复抗瘤免疫反应.
科学领域:
- 免疫学 免疫学 免疫学
- 神经科学是一个神经科学.
- 在瘤学瘤学.
背景情况:
- 癌症免疫逃避通常涉及T细胞上的共抑制受体.
- 目前的免疫疗法只对一小部分患者有益.
- 癌细胞可能采用发育途径,如轴突引导,以逃避免疫监视.
研究的目的:
- 调查癌细胞是否利用轴突引导通路来抑制T细胞免疫力.
- 为了确定参与癌症免疫逃避的特定轴突引导分子.
- 探索针对这些分子的新型癌症免疫治疗策略.
主要方法:
- 利用功能获取遗传选,对人类T细胞上的轴突指导蛋白进行分析.
- 鉴定出富含纤维内素的跨膜蛋白3 (FLRT3) 和它的受体UNC5B.
- 在人性化的癌症模型中测试了FLRT3功能,并评估了抗体阻断的有效性.
主要成果:
- 确定了FLRT3作为一种T细胞抑制性联体,它与UNC5B受体结合,该受体在激活的T细胞上升调节.
- 人类癌症中的FLRT3表达促进了瘤生长,并削弱了CAR-T和BiTE+T细胞介导的杀死和透.
- 一种阻断FLRT3-UNC5B相互作用的单克隆抗体以免疫依赖的方式逆转了促进瘤的效果.
结论:
- 轴导向通路,特别是FLRT3-UNC5B轴,被癌细胞模仿,以创建免疫检查点.
- 针对FLRT3-UNC5B相互作用是增强癌症免疫治疗疗效的有希望的策略.
相关概念视频
Tumor Immunotherapy
524
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.
524
Inhibition of Cdk Activity
4.8K
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...
4.8K
Targeted Cancer Therapies
7.6K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.6K
Mitogens and the Cell Cycle
6.5K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.5K
The Intrinsic Apoptotic Pathway
6.5K
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...
6.5K
Cancer-Critical Genes II: Tumor Suppressor Genes
7.4K
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...
7.4K


