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
STAT1 作为肿瘤中 NK 细胞活化无创监测的工具
英文原题：STAT1 as a tool for non-invasive monitoring of NK cell activation in cancer.
查看英文原题
STAT1 as a tool for non-invasive monitoring of NK cell activation in cancer.
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中文摘要
自然杀伤（NK）细胞能够天然识别并杀伤癌细胞，因此在肿瘤免疫治疗中发挥重要作用。然而，目前在活体内观察 NK 细胞抗肿瘤活性的方法有限。我们提出一种成像方法，通过 STAT1 蛋白无创追踪癌细胞诱导的 NK 细胞激活。为此，我们对 NK 细胞进行改造，使其含有一段在激活时与 STAT1 结合的特定基因序列。通过多种生物学实验和分析，证实这些工程化 NK 细胞（GAS-NK）具有功能。对癌症微环境变化的观察以及患者来源癌症类器官模型的研究进一步验证了该方法的有效性。该方法为监测 NK 细胞活性提供了途径，有望改善对 NK 细胞肿瘤疗法疗效的预测并提高其有效性，推动癌症治疗进步。
展开英文摘要原文
Natural killer (NK) cells play a crucial role in immunotherapy for cancer due to their natural ability to target and destroy cancer cells.
However, current methods to visualize NK cells' activity against tumors in live organisms are limited.
We introduce an imaging method that non-invasively tracks NK cell activation by cancer cells through the STAT1 protein. To achieve this, we modified NK cells to include a specific genetic sequence that binds to STAT1 when activated. These engineered NK cells (GAS-NK) demonstrate their functionality through various biological tests and analysis. Observations of changes in cancer environments and patient-derived cancer organoid models further confirm the effectiveness of this approach.
Our method provides a way to monitor NK cell activity, which could improve the prediction and effectiveness of NK cell-based cancer therapies, contributing to advances in cancer treatment.
论文信息
- 作者
- Min JY、Kim HM、Lee H、Cho MY、Park HS、Lee SY、Park MS、Ha SK
- 第一作者单位
- Biopharmaceutical Research Center, Korea Basic Science Institute (KBSI), Cheongju, 28119, Republic of Korea.South Korea
- 通讯作者单位
- Biopharmaceutical Research Center, Korea Basic Science Institute (KBSI), Cheongju, 28119, Republic of Korea. heh4285@kbsi.re.kr.South Korea
- 文献类型
- 非美国政府资助研究
- 期刊
- Communications biology2024 Sep 30
- 原文标识
- PubMed 39349746 · DOI 10.1038/s42003-024-06917-9
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