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
工程化血小板用于原位 NK 细胞激活以抑制肿瘤复发
英文原题：Engineered Platelet for In Situ Natural Killer Cell Activation to Inhibit Tumor Recurrence.
查看英文原题
Engineered Platelet for In Situ Natural Killer Cell Activation to Inhibit Tumor Recurrence.
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中文摘要
自然杀伤（NK）细胞因其独特的免疫行为，在对抗肿瘤复发方面具有显著优势。与抗体依赖性细胞介导的细胞毒性（ADCC）效应相关的NK细胞疗法已取得显著进展，但仍受限于抗体结合不足以及术后免疫抑制微环境中NK细胞的耗竭状态。利用PLT对肿瘤细胞的黏附特性，我们开发了一种外源性植入的基于血小板（PLT）的NK细胞驱动系统（PLT-IgG-IL15），通过IgG抗体标记提高残留肿瘤的可识别性，以供NK细胞捕获和结合，从而恢复ADCC效应并促进其杀伤功能的恢复。此外，白细胞介素-15（IL-15）参与了NK细胞功能的增强。总体而言，PLT-IgG-IL15既作为NK细胞-肿瘤细胞衔接器，又作为NK细胞充电器，在小鼠肿瘤模型中实现了<40%的复发率。
展开英文摘要原文
Natural killer (NK) cells offer profound advantages against tumor recurrence due to their unique immunological behavior. NK cell therapies associated with the antibody-dependent cell-mediated cytotoxicity (ADCC) effect have made remarkable progress while being limited by insufficient antibody binding and the exhausted state of NK cells in the postsurgical immunosuppressive microenvironment.
Leveraging the adherence of PLT to tumor cells, we developed an exogenously implanted platelet (PLT)-based NK cell-driven system (PLT-IgG-IL15) to improve the identifiability of residual tumors with IgG antibody labeling for NK cells catching and engaging, which consequently restored the ADCC effect and promoted the recovery of their killing function.
Furthermore, interleukin-15 (IL-15) participated in the augmentation of NK cell function. Collectively, PLT-IgG-IL15 served as an NK cell tumor cell engager as well as an NK cell charger, achieving a <40% recurrence rate in mouse tumor models.
论文信息
- 作者
- Deng Y、Tan C、Huang S、Zhou Z、Luo X、Yang X、Sun M
- 单位
- NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Nano letters2024 Sep 25
- 原文标识
- PubMed 39282986 · DOI 10.1021/acs.nanolett.4c02316