与HBV相关的肝细胞癌通过长非编码RNAHDAC2-AS2抑制抗瘤CD8+T细胞
Yanan Gao1, Zhenxing Zhang1, Xuetao Huang1,2
1State Key Laboratory of Epigenetic Regulation and Intervention, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China.
Nature communications
|February 28, 2025
概括
在HBV相关的肝癌中,瘤衍生的细胞外囊泡携带HDAC2-AS2,抑制CD8+T细胞免疫力. 这促进了癌症的进展,但表明HDAC2-AS2作为肝细胞癌的治疗点.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 肝细胞癌 (HCC) 是全球流行的一种恶性瘤.
- 细胞外囊泡 (EVs) 在瘤微环境中调解细胞间通信,经常促进癌症的进展.
- 来自瘤的EV在瘤微环境中的免疫抑制中发挥作用.
研究的目的:
- 调查瘤细胞衍生的EVs在HBV相关的HCC中的作用.
- 在EV中识别有助于免疫抑制的特定分子.
- 探索向这些分子在HCC中的治疗潜力.
主要方法:
- 在HBV相关的HCC中分析瘤细胞衍生的EVs.
- 在EV中识别和表征长非编码RNAHDAC2-AS2.
- 研究HDAC2-AS2对CD8+T细胞的作用机制,包括CDK9转位和T细胞细胞毒性.
- HDAC2-AS2和CDK9表达水平与HCC患者的存活率和对抗PD-1治疗的反应的相关性.
主要成果:
- 与HBV相关的HCC瘤细胞衍生的EVs含有TGFβ诱导的长非编码RNAHDAC2-AS2.2.
- 富含HDAC2-AS2的EV抑制了瘤内CD8+T细胞的细胞毒性.
- HDAC2-AS2抑制了转录因子CDK9在激活的CD8+T细胞中的细胞质转位,导致T细胞耗尽和IFN-γ生产减少.
- 低CDK9和高HDAC2-AS2表达与低HCC存活率相关.
- 抗PD-1疗法可以挽救免疫抑制作用.
结论:
- 来自瘤的EVs通过通过HDAC2-AS2.2抑制抗瘤CD8+T细胞免疫力,从而促进HCC的进展.
- 细胞外HDAC2-AS2是HCC预后的一个潜在生物标志物.
- 准细胞外HDAC2-AS2为HCC提供了一个有希望的治疗策略,可能与免疫疗法结合使用.
更多相关视频
12:09Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
Published on: February 28, 2019
9.7K
10:37Analysis of HBV-Specific CD4 T-cell Responses and Identification of HLA-DR-Restricted CD4 T-Cell Epitopes Based on a Peptide Matrix
Published on: October 20, 2021
2.8K
相关概念视频
01:27Cytotoxic T Cells-mediated Immune Response
825
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
825
01:29Immune Response Against Viral Pathogens
725
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
725
01:27Tumor Immunotherapy
461
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.
461