相关实验视频

Updated: Jun 5, 2025

HPLC-based Assay to Monitor Extracellular Nucleotide/Nucleoside Metabolism in Human Chronic Lymphocytic Leukemia Cells

HPLC-based Assay to Monitor Extracellular Nucleotide/Nucleoside Metabolism in Human Chronic Lymphocytic Leukemia Cells

Published on: July 20, 2016

通过核酸载体ENT1吸收腺素抑制抗瘤免疫力和T细胞皮里米丁合成

David Allard^1,2, Jeanne Cormery^1,2, Salma Bricha^1,2

¹Institut du Cancer de Montréal, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Canada.

Cancer research

|December 9, 2024

概括

阻断平衡核酸转运体-1 (ENT1) 增强了CD8+T细胞的抗瘤免疫力. 这种ENT1阻断抑制了腺驱动的免疫抑制,并加强了癌症PD-1阻断疗法.

科学领域:

免疫学免疫学免疫学
癌症生物学癌症生物学
药理学药理学是指药理学的学科.

背景情况:

氨酸是瘤微环境中的一个关键的免疫抑制分子.
氨酸通过受体和核酸载体发挥其作用.
腺载体在瘤免疫中的作用在很大程度上是未知的.

研究的目的:

研究平衡核酸转运体-1 (ENT1) 在调节瘤免疫力的作用.
为了确定是否准ENT1可以增强抗瘤反应和免疫治疗.

主要方法:

使用ENT1缺乏的小鼠和ENT1.1的药理封锁.
评估了瘤免疫细胞透,基因表达概况和T细胞功能.
研究了T细胞中ENT1-介导免疫抑制的分子机制.

主要成果:

ENT1 缺陷显著增强了 CD8+ T 细胞依赖的抗瘤免疫力.
缺少ENT1的瘤显示效应性CD8+T细胞增加,抑制调节性T细胞和免疫抑制性巨细胞.
阻断ENT1增强了PD-1阻断的有效性,并增强了T细胞的功能.
通过ENT1介导的腺摄取抑制了T细胞代谢,通过抑制酸酸合成酶.

结论:

在癌症中,ENT1是腺诱导的免疫抑制的关键媒介.
向ENT1代表了增强抗瘤T细胞反应的有希望的策略.
ENT1阻塞可以克服免疫抑制,并提高检查点抑制剂 (如PD-1阻塞) 的疗效.

更多相关视频

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1

Published on: April 16, 2021

相关概念视频

Biosynthesis of Nucleic Acids

Biosynthesis of Nucleic Acids

Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...

Allosteric Proteins-ATCase

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...

Tumor Immunotherapy

Tumor Immunotherapy

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.

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy. SP binds and activates...

Treatment Resistant Cancers

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...

Desensitization and Tachyphylaxis

Desensitization and Tachyphylaxis

Tachyphylaxis is described as a rapid decrease in response to a drug after repeated or continuous administration of the same drug dose. It is a phenomenon where the body becomes less responsive to a particular substance or intervention over time, requiring higher doses or stronger interventions to achieve the same effect. It results from adaptive changes in the body's receptors, signaling pathways, or physiological processes that occur in response to prolonged exposure to a stimulus.