RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
索拉非尼抑制肝细胞癌中浆细胞样树突状细胞产生干扰素
英文原题：Sorafenib inhibits interferon production by plasmacytoid dendritic cells in hepatocellular carcinoma.
查看英文原题
Sorafenib inhibits interferon production by plasmacytoid dendritic cells in hepatocellular carcinoma.
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研究概要
索拉非尼抑制了 pDCs 功能。鉴于索拉非尼是目前推荐的抗癌靶向治疗药物，我们的结果表明，在治疗过程中应考虑其对 pDCs 的免疫抑制作用。
研究思路结论见上方概要
背景
索拉非尼是一种多激酶抑制剂，在晚期肝细胞癌中显示出抗肿瘤活性。索拉非尼对免疫细胞发挥调节作用，包括T细胞、NK 细胞和树突状细胞。研究表明，浆细胞样树突状细胞（pDCs）在癌症组织中功能受损，或在癌症微环境中产生较低水平的I型干扰素α（IFNα）。然而，索拉非尼对pDCs功能的影响尚未得到详细评估。
方法
正常和患者的PBMC用CpG-A刺激，通过流式细胞术和ELISA评估IFNα的产生。
结果
我们分析了在接受索拉非尼治疗的晚期HCC患者中，PBMCs产生IFNα的情况。我们发现，接受索拉非尼治疗的HCC患者产生的IFNα少于未治疗的患者。此外，我们证明索拉非尼以浓度依赖的方式抑制了健康供者PBMCs或pDCs产生IFNα。
展开英文摘要原文
BACKGROUND
Sorafenib is a multi-kinase inhibitor that shows antitumor activity in advanced hepatocellular carcinoma. Sorafenib exerts a regulatory effect on immune cells, including T cells, natural killer cells and dendritic cells. Studies have shown that plasmacytoid dendritic cells (pDCs) are functionally impaired in cancer tissues or produce low type I interferon alpha (IFNα) in cancer microenvironments. However, the effects of sorafenib on the function of pDCs have not been evaluated in detail.
METHODS
Normal and patient PBMCs were stimulated with CpG-A to evaluate IFNα production with Flow cytometry and ELISA. RESULT: We analyzed the production of IFNα by PBMCs in patients with advanced HCC under sorafenib treatment. We found that sorafenib-treated HCC patients produced less IFNα than untreated patients. Furthermore, we demonstrated that sorafenib suppressed the production of IFNα by PBMCs or pDCs from heathy donors in a concentration-dependent manner.
CONCLUSION
Sorafenib suppressed pDCs function. Given that sorafenib is a currently recommended targeted therapeutic agent against cancer, our results suggest that its immunosuppressive effect on pDCs should be considered during treatment.
论文信息
- 作者
- Zhang X、Xu Y、Zhao G、Liu R、Yu H
- 第一作者单位
- Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital, Beijing, China.China
- 通讯作者单位
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China. yu_haisheng@hotmail.com.China
- 期刊
- BMC cancer2022 Nov 30
- 原文标识
- PubMed 36451110 · DOI 10.1186/s12885-022-10356-2
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