CD47的化调节了先天的抗瘤免疫反应
Qian Gou1, Bingjun Yan1, Yalan Duan1
1School of Life Science, Jiangsu University, Zhenjiang, Jiangsu Province, 212013, People's Republic of China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|December 12, 2024
概括
瘤细胞通过SIRPα/CD47检查点逃避免疫反应. 由TRAF2诱导的CD47无化阻断了降解,促进了免疫逃逸,并阻碍了抗瘤疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- SIRPα/CD47轴是一个关键的先天性免疫检查点,调节瘤免疫逃逸.
- 了解CD47无处不在在瘤免疫逃脱中的作用至关重要.
研究的目的:
- 为了阐明CD47无处不在的机制有助于瘤免疫逃生.
- 调查TRAF2在CD47无化中的作用以及随后对巨细胞细胞的作用.
主要方法:
- 同免疫沉试验检测到TRAF2与CD47结合.
- 西部涂抹以评估CD47的无处不在和降解.
- 自试验评估对LC3结合和自流动的影响.
- 巨细胞化试验. 大细胞化试验.
- 在体内瘤模型评估免疫逃脱和治疗疗效.
主要成果:
- TRAF2与CD47的细胞质尾部结合,从而诱导其无处不在.
- 乌比基化CD47显示与LC3的结合减少,抑制其自降解.
- 通过TRAF2介导的CD47无处置会损害巨细胞化,促进瘤免疫逃生.
- 丢失TRAF2增强CD47自降解,并抑制瘤免疫逃生.
- 自诱导促进了CD47的降解,并提高了CD47抗体治疗的疗效.
结论:
- 由TRAF2诱导的CD47无处可见性代表了通过抑制自细胞降解和巨细胞灭菌的瘤免疫逃逸的新机制.
- 向TRAF2或增强自可能是克服CD47介导免疫抵抗和改善免疫治疗结果的潜在策略.
相关概念视频
Abnormal Proliferation
4.4K
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...
4.4K
The Intrinsic Apoptotic Pathway
6.4K
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...
6.4K
Receptor Downregulation in MVBs
2.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.0K
Tumor Immunotherapy
476
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.
476
The Extrinsic Apoptotic Pathway
6.3K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.3K
Inhibition of Cdk Activity
4.7K
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...
4.7K


