多omics分析显示,胆酸介导的免疫抑制是由肝细胞癌中瘤口腔管状反应驱动的
Qianhui Xu1, Hang Chen2, Ganggang Wang2
1Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China; Department of Hepatobiliary Surgery and Liver Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China.
Cancer letters
|March 4, 2026
概括
在肝细胞癌中,导管反应预示着不良结果. 通过NR1H4抑制和抗PD1疗法向胆酸/NR1H4通路显示出抑制瘤生长的前景.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
背景情况:
- 肝细胞癌 (HCC) 是全球主要的癌症死亡原因.
- 周微环境相互作用显著影响HCC的进展.
- 导管反应是HCC微环境的关键组成部分.
研究的目的:
- 通过使用多omics方法来表征HCC中周腔管状反应.
- 为了研究管状反应的预后意义.
- 在管状反应微环境中识别治疗点.
主要方法:
- 人工智能-病理学,单核多态学,空间转录学和代谢学.
- 对状反应评分的分析以及与临床结果和肝硬化严重程度的相关性.
- 胆细胞亚种群的识别和功能性特征.
- 瘤边缘的代谢分析和胆酸对免疫细胞影响的研究.
- 使用小鼠模型进行NR1H4抑制和抗PD1治疗的体内研究.
主要成果:
- 导管反应得分强烈预测了不良的临床结果,并与肝硬化严重程度相关.
- 鉴定出了三种不同的胆血管细胞亚群,其中一种亚型显示出显著的纤维细胞相互作用,促进了 stromal 重塑.
- 在瘤边缘的胆酸丰富通过NR1H4依赖的PD1上调诱导了CD8+T细胞功能障碍.
- 与抗PD1治疗相结合的NR1H4抑制在小鼠模型中显著抑制了瘤生长.
结论:
- 导管反应作为肝细胞癌的预后生物标志物.
- 胆酸/NR1H4通路是HCC免疫抑制的关键调解者.
- 向胆酸/NR1H4通路对HCC患者来说是一个有前途的免疫治疗策略.
更多相关视频
相关概念视频
01:29Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
616
Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
616
01:29Drugs for Treatment of Ulcerative Colitis in IBD
578
Ulcerative colitis is a chronic inflammatory condition primarily affecting the colon and rectum. The primary drugs used in the treatment of ulcerative colitis are aminosalicylates. They exhibit anti-inflammatory and immunosuppressive properties. They modulate inflammatory mediators and inhibit the activity of nuclear factor κB (NF-κB). Aminosalicylates also reduce inflammation by inhibiting prostaglandin and leukotriene production and decreasing neutrophil chemotaxis and superoxide...
578
01:21Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids
582
Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2...
582
01:26Diseases of the Liver and Gallbladder
2.2K
Liver and gallbladder diseases are a significant health concern, with prominent conditions including cirrhosis, hepatitis, non-alcoholic fatty liver disease (NAFLD), and gallstones. Jaundice is a common manifestation of liver and biliary disease.
Cirrhosis is characterized by the scarring of hepatic lobules in the liver, which are replaced by fibrous tissue, affecting the liver's normal functioning. NAFLD, on the other hand, is caused by an excessive build-up of fat in the liver, not...
Cirrhosis is characterized by the scarring of hepatic lobules in the liver, which are replaced by fibrous tissue, affecting the liver's normal functioning. NAFLD, on the other hand, is caused by an excessive build-up of fat in the liver, not...
2.2K
01:26Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow
304
Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug...
304
01:28Acid Suppressive Drugs for Peptic Ulcer Disease: Histamine H2-Receptor Antagonists
1.1K
Histamine H2 receptors, which are intricately located on the basolateral membrane of parietal cells, play a crucial role in modulating gastric acid secretion. When released from enterochromaffin-like cells, histamine engages H2 receptors, initiating the cyclic AMP (cAMP) pathway. In this pathway, adenylyl cyclase converts ATP into cAMP, elevating intracellular cAMP levels. The activation of protein kinase A follows, stimulating the proton pump. This stimulation prompts the secretion of hydrogen...
1.1K