解码瘤微环境:外体介导的巨细胞极化和治疗边界
Yilin Li1, Jiaqi You2, Zifang Zou1
1Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang 110002, China.
International journal of biological sciences
|July 4, 2025
概括
由瘤衍生的外体,在低氧和ERS下由HIF-1α调节,调节巨细胞两极分化和免疫逃避. 工程外体具有针对瘤微环境相互作用的癌症免疫疗法的潜力.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 瘤微环境 (TME) 涉及复杂的相互作用,与瘤相关的巨细胞 (TAMs) 在癌症进展中发挥关键作用.
- 外体细胞介导细胞间通信,并对调节TME内的巨细胞极化至关重要.
- 缺氧和内分泌网膜应激 (ERS) 显著影响瘤细胞的行为和外体细胞的产生.
研究的目的:
- 系统地审查缺氧诱导因子1-alpha (HIF-1α) 在低氧条件下调节瘤衍生的外体的作用.
- 阐明在ERS下涉及外体生物发生和分泌的分子通路 (STAT3,PI3K/AKT/mTOR,HSP90/Hippo).
- 评估TAM衍生的外体在免疫逃避,转移以及它们与其他TME组件的相互作用中的参与,并讨论免疫治疗的外体工程策略.
主要方法:
- 对瘤衍生异构体,HIF-1α,巨细胞极化和相关信号通路的现有文献进行系统审查.
- 分析分子机制,包括LncRNA HMMR-AS1,特定的miRNAs (miR-1246,let-7a,miR-301a-3p,miR-23a-3p,miR-27a-3p) 和PD-L1的表达.
- 评估TME内的外体与免疫细胞 (CD8+ T细胞) 和肌体成分 (纤维细胞) 的相互作用.
主要成果:
- 在缺氧下,HIF-1α被确定为瘤衍生的外体的中央调节者.
- 通过Hsp90/Hippo无活化,ERS激活STAT3和PI3K/AKT/mTOR通路,诱导特定的lncRNAs和miRNAs,这些RNAs会影响外体的内容.
- 外基因组携带miRNAs和PD-L1,促进M2巨细胞两极化,免疫逃避和转移;证实了与TME组件的双向交叉通话.
结论:
- 瘤衍生的外基因组,特别是那些受低氧和ERS影响的外基因组,是塑造TME和促进癌症进展的关键参与者.
- 了解外体分泌和内容的分子调节对于开发向癌症疗法至关重要.
- 外体工程策略与先进的奥米克和人工智能相结合,有望将外体转化为有效的临床免疫疗法方案,尽管仍然存在挑战.
相关概念视频
02:17The Tumor Microenvironment
6.8K
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...
6.8K
01:27Tumor Immunotherapy
665
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.
665
01:36Overview of Exosomes
2.9K
Exosomes are stable, lipid bilayer-enclosed vesicles capable of crossing biological barriers. They can carry a wide range of molecules required for intercellular communication. Once exosomes are released from the cell where they originated, they enter a recipient cell through various pathways such as fusion, receptor-mediated endocytosis, macropinocytosis, and phagocytosis.
Stahl et al. discovered exosomes in 1983, but the exosomes were initially considered waste products released from the...
Stahl et al. discovered exosomes in 1983, but the exosomes were initially considered waste products released from the...
2.9K
02:57Targeted Cancer Therapies
7.8K
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...
7.8K