ASMase对于对部分瘤辐射暴露的免疫反应至关重要
Mickael Mathieu1,2, Prerna R Nepali2, James Russell3
1Clinical Research Unit, Emile Roux Hospital Center, Le Puy-en-Velay, France.
概括
酸髓酶 (ASMase) 和胺生成对于放射治疗来激活抗瘤免疫反应至关重要. 这种通过STING介导的免疫激活对于放射治疗后有效的瘤控制至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 生物化学 生物化学
背景情况:
- 瘤对放射治疗的反应传统上归因于直接杀死瘤细胞.
- 宿主生物学,特别是内皮酸髓酶 (ASMase) 表达,极大地影响瘤的放射治疗能力.
- 免疫系统可以增强辐射反应,在部分辐射的瘤中实现完全的瘤控制.
研究的目的:
- 调查宿主ASMase活动和免疫系统参与辐射治疗反应的整合.
- 阐明ASMase在调解辐射诱导的抗瘤免疫中的作用.
主要方法:
- 易斯肺癌 (LLC) 细胞植入ASMase淘汰赛 (KO) 和野生型 (WT) 小鼠.
- 辐射疗法 (RT) 输送到瘤体积的50%或100%.
- 评估了瘤反应,CD8+ T细胞透,ICAM-1表达和STING激活. 通过使用甲基-环德克斯特林,ASMase在药理上被抑制.
主要成果:
- 在WT小鼠中,半辐射有效控制了瘤,但在ASMase KO小鼠中没有.
- 药理上抑制ASMase显著降低了瘤对半辐射的反应.
- 在WT小鼠的瘤中观察到高的ICAM-1,CD8+T细胞和STING激活,但不是ASMase KO小鼠的瘤.
结论:
- 酸髓酶 (ASMase) 和胺生成是辐射诱导的抗瘤免疫反应所必需的.
- 针激活是这种ASMase依赖辐射免疫反应的关键调解者.
- 这些发现凸显了宿主ASMase在利用免疫系统进行有效的癌症放射治疗方面的关键作用.
更多相关视频
05:08Targeted and Selective Treatment of Pluripotent Stem Cell-derived Teratomas Using External Beam Radiation in a Small-animal Model
Published on: February 17, 2019
6.1K
11:24Measuring DNA Damage and Repair in Mouse Splenocytes After Chronic In Vivo Exposure to Very Low Doses of Beta- and Gamma-Radiation
Published on: July 3, 2015
11.0K
相关概念视频
The Tumor Microenvironment
6.6K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.6K
Mutations
35.1K
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
35.1K
Tumor Immunotherapy
491
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.
491
DNA Damage can Stall the Cell Cycle
9.1K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.1K
Targeted Cancer Therapies
7.5K
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...
7.5K
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
![Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate DMBA-TPA](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F60445.jpg&w=3840&q=50)