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:Designable Nanoadaptor for Enhanced Recognition of Natural Killer Cell to Tumor via Bio-orthogonal Click Reaction.
Designable Nanoadaptor for Enhanced Recognition of Natural Killer Cell to Tumor via Bio-orthogonal Click Reaction.
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免疫细胞对癌细胞的高效识别对于成功的基于治疗性细胞的癌症免疫治疗至关重要。在此,我们提出了一种简便的NIR-II纳米适配器[透明质酸(HA)/二苯并环辛炔(DBCO)-Au:Ag 2 Te量子点(QDs)],通过体内生物正交点击反应用于增强自然杀伤(NK)细胞对肿瘤的识别和结合能力。该纳米适配器具有优越的肿瘤靶向能力,促进化学受体DBCO在肿瘤部位的积累。随后,DBCO在肿瘤细胞表面的富集提供了多价识别位点,通过高效的点击反应捕获预处理的叠氮化物工程化NK92细胞(NK92-N 3 ),从而显著提高治疗效率。在小鼠肺癌模型中,通过多重NIR-II荧光成像可以生动地观察到纳米适配器介导的NK细胞对肿瘤细胞识别的动态过程。这种纳米适配器策略可以扩展到其他治疗性细胞系统,并有望用于未来的临床应用。
Highly efficient recognition of cancer cells by immune cells is important for successful therapeutic-cell-based cancer immunotherapy.
Herein, we present a facile NIR-II nanoadaptor [hyaluronic acid (HA)/dibenzocyclooctyne (DBCO)-Au:Ag 2 Te quantum dots (QDs)] for enhancing the tumor recognition and binding ability of natural killer (NK) cells via a bio-orthogonal click reaction in vivo. The Nanoadaptor possesses superior tumor-targeting capacity, facilitating the accumulation of the chemical receptor DBCO at the tumor sites.
Subsequently, the enrichment of DBCO on tumor cell surfaces provides multivalent recognition sites for capturing pretreated azide engineered NK92 cells (NK92-N 3 ) through an efficient click reaction, thereby significantly enhancing the therapeutical efficiency.
The dynamic process of nanoadaptor-mediated recognition of NK cells to tumor cells could be vividly observed using multiplexed NIR-II fluorescence imaging in a mouse model of lung cancer. Such a nanoadaptor strategy can be extended to other therapeutic cellular systems and holds promise for future clinical applications.
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