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
英文原题:Effect of surface modification on the distribution of magnetic nanorings in hepatocellular carcinoma and immune cells.
Effect of surface modification on the distribution of magnetic nanorings in hepatocellular carcinoma and immune cells.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
磁性纳米材料介导的磁热疗是一种局部加热治疗方式,已在临床上用于治疗侵袭性癌症。除了被肿瘤细胞摄取以发挥癌症治疗作用外,磁性纳米材料还可被肿瘤微环境中的免疫细胞内化,这可能有助于调节抗肿瘤免疫效应。
然而,关于磁性纳米材料在肿瘤组织内不同类型细胞中分布的研究很少。在此,成功合成了带有或不带有肝癌靶向肽SP94的亚铁磁性涡旋畴氧化铁纳米环(FVIOs)作为模型系统,以研究FVIOs表面修饰(带或不带SP94)对小鼠肝细胞癌(HCC)微环境中肿瘤细胞和不同免疫细胞分布的影响。FVIO-SP94s在肿瘤细胞中的分布比例是FVIOs的1.3倍。肝脏肿瘤微环境中的免疫细胞对FVIO-SP94s的摄取少于FVIOs。
此外,发现髓系细胞在吞噬纳米颗粒的能力方面比淋巴系细胞强得多。具体而言,FVIOs/FVIO-SP94s在肿瘤相关巨噬细胞、树突状细胞和髓源性抑制细胞中的分布分别为13.8%/12%、3.7%/0.9%和6.3%/1.2%。而FVIOs/FVIO-SP94s在T细胞、B细胞和NK 细胞中的分布分别为5.5%/0.7%、3.0%/0.7%和0.4%/0.3%。本文所述结果加深了我们对纳米材料在肿瘤微环境中分布的理解,并为合理设计能够有效调控抗肿瘤免疫效应的磁热疗剂提供了策略。
Magnetic nanomaterial-mediated magnetic hyperthermia is a localized heating treatment modality that has been applied to treat aggressive cancer in clinics.
In addition to being taken up by tumor cells to function in cancer therapy, magnetic nanomaterials can also be internalized by immune cells in the tumor microenvironment, which may contribute to regulating the anti-tumor immune effects.
However, there exists little studies on the distribution of magnetic nanomaterials in different types of cells within tumor tissue.
Herein, ferrimagnetic vortex-domain iron oxide nanorings (FVIOs) with or without the liver-cancer-targeting peptide SP94 have been successfully synthesized as a model system to investigate the effect of surface modification of FVIOs (with or without SP94) on the distribution of tumor cells and different immune cells in hepatocellular carcinoma (HCC) microenvironment of a mouse. The distribution ratio of FVIO-SP94s in tumor cells was 1. 3 times more than that of FVIOs. Immune cells in the liver tumor microenvironment took up fewer FVIO-SP94s than FVIOs.
In addition, myeloid cells were found to be much more amenable than lymphoid cells in terms of their ability to phagocytose nanoparticles. Specifically, the distributions of FVIOs/FVIO-SP94s in tumor-associated macrophages, dendritic cells, and myeloid-derived suppressor cells were 13. 8%/12%, 3. 7%/0. 9%, and 6. 3%/1. 2%, respectively.
While the distributions of FVIOs/FVIO-SP94s in T cells, B cells, and natural killer cells were 5. 5%/0. 7%, 3. 0%/0. 7%, and 0. 4%/0. 3%, respectively. The results described in this article enhance our understanding of the distribution of nanomaterials in the tumor microenvironment and provide a strategy for rational design of magnetic hyperthermia agents that can effectively regulate anti-tumor immune effects.
MEMBER ACCOUNT
登录成功会直接打开下一页。