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
纳米级重构免疫突触与衔接器增强 NK 细胞功能
英文原题：Nanoscale restructuring of the immune synapse with an engager enhances NK cell function.
查看英文原题
Nanoscale restructuring of the immune synapse with an engager enhances NK cell function.
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。
中文摘要
Engager 是基于抗体的疗法，可结合免疫细胞受体和靶细胞配体。下一代 engager 通常结合两个激活受体，但其对免疫突触形成和信号传导的影响尚不清楚。在此，我们用一种结合 CD33 的抗急性髓系白血病 engager 在NK 细胞上共连接激活受体 CD16a 和 NKG2D。超分辨率显微镜显示，用单个分子共连接 CD16a 和 NKG2D 触发了它们的纳米级共聚集。这增强了 CD3ζ、ZAP70 和 SLP-76 的磷酸化，从而增加了来自健康供者和 AML 患者的 NK 细胞分泌 IFN-γ 和 TNF-α。因此，除了将免疫细胞与靶细胞连接外，engager 的临床前景还源于其操纵免疫突触纳米级结构的能力。
展开英文摘要原文
Engagers are antibody-based therapies which bind immune cell receptors and a target cell ligand. Next-gen engagers typically bind two activating receptors, but the effect of this on immune synapse formation and signaling is unknown.
Here, we coligated activating receptors CD16a and NKG2D on natural killer (NK) cells with a CD33-binding anti-acute myeloid leukemia (AML) engager. Superresolution microscopy revealed that coligating CD16a and NKG2D with a single molecule triggered their nanoscale coclustering. This enhanced phosphorylation of CD3ζ, ZAP70, and SLP-76 which augmented secretion of IFN-γ and TNF-α, by NK cells from healthy donors and AML patients.
Thus, in addition to connecting immune cells to target cells, the clinical promise of engagers results from their ability to manipulate the nanoscale architecture of the immune synapse.
论文信息
- 作者
- Hazime KS、Sheppard S、Niembro-Vivanco O、Hosty C、Thomas H、Loosbroock C、Peiser L、Davis DM
- 单位
- Department of Life Sciences, Sir Alexander Fleming Building, Imperial College London, South Kensington, London SW7 2AZ, United Kingdom.United Kingdom
- 期刊
- Proceedings of the National Academy of Sciences of the United States of America2025 Sep 23
- 原文标识
- PubMed 40966288 · DOI 10.1073/pnas.2507336122
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →