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:Engineering CaP-Pickering emulsion for enhanced mRNA cancer vaccines via dual DC and NK activations.
Engineering CaP-Pickering emulsion for enhanced mRNA cancer vaccines via dual DC and NK activations.
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mRNA递送系统,如脂质纳米颗粒(LNP),在提高mRNA表达方面已取得显著进展,而免疫系统激活则存在阈值效应。维持抗原表达与树突状细胞(DC)激活之间的微妙平衡对于有效的免疫识别至关重要。在此,开发了一种由磷酸钙纳米颗粒稳定的水包油包水(w/o/w)Pickering乳液(CaP-PME),用于癌症疫苗中的mRNA递送。CaP-PME能有效地将mRNA转运至细胞质,通过破坏细胞内钙/钾离子平衡诱导促炎反应并激活DC。与LNP不同,CaP-PME表现出对DC的偏好性,增强其激活及向淋巴结的迁移。它引发干扰素-γ介导的CD8+ T细胞反应,并促进NK细胞增殖和激活,导致明显的NK细胞浸润和肿瘤微环境改善。所制备的w/o/w Pickering乳液在E.G7和B16-OVA肿瘤模型中表现出优越的抗肿瘤效果,作为癌症疫苗的增强型mRNA递送载体具有广阔前景。
mRNA delivery systems, such as lipid nanoparticle (LNP), have made remarkable strides in improving mRNA expression, whereas immune system activation operates on a threshold. Maintaining a delicate balance between antigen expression and dendritic cell (DC) activation is vital for effective immune recognition.
Here, a water-in-oil-in-water (w/o/w) Pickering emulsion stabilized with calcium phosphate nanoparticles (CaP-PME) is developed for mRNA delivery in cancer vaccination. CaP-PME efficiently transports mRNA into the cytoplasm, induces pro-inflammatory responses and activates DCs by disrupting intracellular calcium/potassium ions balance. Unlike LNP, CaP-PME demonstrates a preference for DCs, enhancing their activation and migration to lymph nodes.
It elicits interferon-γ-mediated CD8 + T cell responses and promotes NK cell proliferation and activation, leading to evident NK cells infiltration and ameliorated tumor microenvironment. The prepared w/o/w Pickering emulsion demonstrates superior anti-tumor effects in E. G7 and B16-OVA tumor models, offering promising prospects as an enhanced mRNA delivery vehicle for cancer vaccinations.
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