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
英文原题:Efficacy of natural killer cell therapy combined with chemoradiotherapy in murine models of head and neck squamous cell carcinoma.
Efficacy of natural killer cell therapy combined with chemoradiotherapy in murine models of head and neck squamous cell carcinoma.
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识别 NK 细胞配体在 CRT 期间的激活模式可能改善患者对辅助 NK 细胞免疫治疗联合 CRT 的选择。这是首个在 HNSCC 小鼠模型中研究 NK 细胞抗肿瘤功能及 CRT 招募的研究。
基于NK细胞的肿瘤免疫治疗与放疗和化疗等其他治疗方式联合使用时有效。NK细胞治疗实体瘤(包括头颈部鳞状细胞癌(HNSCC))的抗肿瘤功能近来已成为靶向研究对象。本研究评估了HNSCC中化放疗(CRT)后NK细胞的募集情况。
进行了NK细胞体外扩增、流式细胞术、细胞活力测定、细胞毒性测定、免疫组织化学和动物模型实验。
在小鼠裸鼠模型中,CRT将小鼠NK细胞招募至肿瘤部位。此外,在NOD/SCID IL-2R null小鼠模型中,扩增并激活的人NK细胞(eNKs)响应CRT被招募至肿瘤部位,且CRT增强了eNK的抗肿瘤活性。多种HNSCC癌细胞系在响应CRT时表现出不同的NK细胞配体激活模式,这些模式与NK细胞介导的细胞毒性相关。
Ex vivo expansion of NK cell, flow cytometry, cell viability assay, cytotoxicity assay, immunohistochemistry, and animal model were performed.
Mouse NK cells were recruited to the tumor site by CRT in a nude mouse model. Furthermore, expanded and activated human NK cells (eNKs) were recruited to the tumor site in response to CRT, and CRT enhanced the anti-tumor activity of eNK in an NOD/SCID IL-2R null mouse model. Various HNSCC cancer cell lines exhibited different NK cell ligand activation patterns in response to CRT that correlated with NK cell-mediated cytotoxicity.
Identifying the activation patterns of NK cell ligands during CRT might improve patient selection for adjuvant NK cell immunotherapy combined with CRT. This is the first study to investigate the NK cell's antitumor function and recruitment with CRT in HNSCC mouse model.
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