低氧诱导免疫抑制通过沉默癌症中的刺诱导免疫抑制
Yuhong Lu1, Annali M Yurkevicz1, Yanfeng Liu1
1Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.
Cancer research
|September 12, 2025
概括
瘤缺氧通过HIF1α,KDM1A和KDM5A使STING沉默,这是一个关键的免疫路径. 准KDM1A可以恢复STING,从而有可能改善癌症疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 分子瘤学分子瘤学
背景情况:
- 刺激IFN基因 (STING) 对于抗瘤免疫至关重要,但在癌症中经常被沉默.
- 瘤缺氧是一种常见的特征,可以抑制抗癌免疫反应.
研究的目的:
- 研究瘤缺氧在调节STING表达中的作用及其对癌症免疫力的影响.
- 为了确定低氧诱导的STING沉默背后的分子机制.
- 探索针对STING重新激活的治疗策略.
主要方法:
- 在低氧条件下分析各种癌症类型中STING表达的分析.
- 研究HIF1α,KDM1A和KDM5A在STING调节中的作用.
- 使用小鼠模型进行体内研究,以评估KDM1A抑制的有效性.
主要成果:
- 瘤缺氧以依赖HIF1α的方式降低STING的调节.
- STING沉默与KDM1A/KDM5A的表观遗传修饰和对代谢物失调有关.
- 抑制KDM1A逆转了缺氧诱导的STING降低调节,并在体内增强了抗瘤免疫反应.
结论:
- 缺氧,表观遗传修饰剂 (KDM1A/KDM5A) 和代谢物相互作用抑制STING介导的抗瘤免疫力.
- 向KDM1A是一个有希望的策略,可以恢复STING通路的活性,并提高癌症治疗的疗效.
相关概念视频
Adaptive Mechanisms in Cancer Cells
7.0K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
7.0K
Regulation of Angiogenesis and Blood Supply
3.3K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.3K
Cancer Therapies
9.8K
Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
9.8K
Regulation of Hematopoietic Stem Cells
4.0K
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
4.0K
The Tumor Microenvironment
7.6K
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...
7.6K
Tumor Immunotherapy
1.8K
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.
1.8K


