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
利用 lncRNA NeST 选择性增强的 YTS 细胞清除 CD48 阳性肿瘤
英文原题：Eradication of CD48-positive tumors by selectively enhanced YTS cells harnessing the lncRNA NeST.
查看英文原题
Eradication of CD48-positive tumors by selectively enhanced YTS cells harnessing the lncRNA NeST.
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
自然杀伤（NK）细胞目前已用于肿瘤治疗临床试验，但此类疗法仍存在供者差异、重复性等问题，阻碍了 NK 细胞疗法的更广泛应用。
本研究展示了一种结合 NK 细胞介导的肿瘤清除与长链非编码 RNA 的潜在免疫疗法。研究在类 NK 细胞系 YTS 中过表达可增强干扰素（IFN）分泌的长链非编码 RNA——nettoie Salmonella pas Theiler's（NeST）。YTS 细胞表达共刺激受体 2B4，其主要配体为 CD48；在 YTS 细胞中，2B4 通过直接激活发挥作用。研究显示，YTS 细胞过表达 NeST 后，与 CD48 相互作用时 IFN 释放增加，形成选择性增强的 YTS 细胞（seYTS）。经照射后，seYTS 失去增殖能力，但仍能维持杀伤和分泌 IFN 的能力。
最后，研究证实经照射的 seYTS 可在体内抑制肿瘤生长。因此，我们提出 seYTS 细胞可能成为针对 CD48 表达肿瘤的现成型疗法。
展开英文摘要原文
Natural killer (NK) cells are currently used in clinical trials to treat tumors.
However, such therapies still suffer from problems such as donor variability, reproducibility, and more, which prevent a wider use of NK cells therapeutics.
Here we show a potential immunotherapy combining NK cell-mediated tumor eradiation and long non-coding (lnc) RNAs.
We overexpressed the interferon (IFN) secretion-enhancing lncRNA nettoie Salmonella pas Theiler's (NeST) in the NK cell-like cell line YTS. YTS cells express the co-stimulatory receptor 2B4 whose main ligand is CD48. On YTS cells, 2B4 functions by direct activation.
We showed that NeST overexpression in YTS cells resulted in increased IFN release upon interaction with CD48 (selectively enhanced (se)YTS cells). Following irradiation, the seYTS cells lost proliferation capacity but were still able to maintain their killing and IFN secretion capacities.
Finally, we demonstrated that irradiated seYTS inhibit tumor growth in vivo .
Thus, we propose seYTS cells as off-the-shelve therapy for CD48-expressing tumors.
论文信息
- 作者
- Kotzur R、Stein N、Kahlon S、Berhani O、Isaacson B、Mandelboim O
- 单位
- The Lautenberg Center for Immunology and Cancer Research, the Hebrew University, Medical School Hadassah Ein Karem, Israel, Jerusalem.Israel
- 期刊
- iScience2023 Aug 18
- 原文标识
- PubMed 37609636 · DOI 10.1016/j.isci.2023.107284
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 →