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
静脉输注 NK 细胞在原位胶质母细胞瘤异种移植小鼠模型中的抗肿瘤作用及基因表达谱分析
英文原题：Antitumor Effects of Intravenous Natural Killer Cell Infusion in an Orthotopic Glioblastoma Xenograft Murine Model and Gene Expression Profile Analysis.
查看英文原题
Antitumor Effects of Intravenous Natural Killer Cell Infusion in an Orthotopic Glioblastoma Xenograft Murine Model and Gene Expression Profile Analysis.
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中文摘要
尽管采用了标准的多模式治疗，包括最大安全范围切除、替莫唑胺、放疗和肿瘤电场治疗，胶质母细胞瘤（GBM）患者的预后仍然极差。基于NK 细胞（NKC）的免疫治疗在GBM治疗中可能发挥关键作用。
我们此前已报道了来源于人外周血的高度活化和体外扩增的NK细胞，其对GBM细胞表现出抗肿瘤效应。在此，我们利用体内原位异种移植模型——NOD/Shi-scid, IL-2R KO（NOG）小鼠中U87MG细胞来源的脑肿瘤——对NK细胞进行了临床前评估。在原位异种移植模型中，经眶后静脉注射NK细胞延长了NOG小鼠的总生存期，间接表明NK细胞具有生长抑制作用。
此外，我们通过微阵列全面总结了经NKC治疗与未经药物治疗的小鼠脑肿瘤之间的差异表达基因，特别关注了NKC活化受体配体、抑制性受体配体、趋化因子和趋化因子受体的表达。
进一步地，我们还对原位异种移植模型中内部与外部脑肿瘤进行了差异表达基因分析。我们的发现可为GBM患者的NK细胞免疫治疗提供关键信息。
展开英文摘要原文
Despite standard multimodality treatment, containing maximum safety resection, temozolomide, radiotherapy, and a tumor-treating field, patients with glioblastoma (GBM) present with a dismal prognosis. Natural killer cell (NKC)-based immunotherapy would play a critical role in GBM treatment.
We have previously reported highly activated and ex vivo expanded NK cells derived from human peripheral blood, which exhibited anti-tumor effect against GBM cells.
Here, we performed preclinical evaluation of the NK cells using an in vivo orthotopic xenograft model, the U87MG cell-derived brain tumor in NOD/Shi-scid, IL-2R KO (NOG) mouse. In the orthotopic xenograft model, the retro-orbital venous injection of NK cells prolonged overall survival of the NOG mouse, indirectly indicating the growth-inhibition effect of NK cells.
In addition, we comprehensively summarized the differentially expressed genes, especially focusing on the expression of the NKC-activating receptors' ligands, inhibitory receptors' ligands, chemokines, and chemokine receptors, between murine brain tumor treated with NKCs and with no agents, by using microarray.
Furthermore, we also performed differentially expressed gene analysis between an internal and external brain tumor in the orthotopic xenograft model.
Our findings could provide pivotal information for the NK-cell-based immunotherapy for patients with GBM.
论文信息
- 作者
- Morimoto T、Nakazawa T、Matsuda R、Maeoka R、Nishimura F、Nakamura M、Yamada S、Park YS
- 单位
- Department of Neurosurgery, Nara Medical University, Kashihara 634-8521, Nara, Japan.Japan
- 期刊
- International journal of molecular sciences2024 Feb 19
- 原文标识
- PubMed 38397112 · DOI 10.3390/ijms25042435
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