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:The prospect of genetically engineering natural killer cells for cancer immunotherapy.
The prospect of genetically engineering natural killer cells for cancer immunotherapy.
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自然杀伤(NK)细胞在癌症免疫治疗中的应用展现出广阔前景,但其疗效常因体内杀伤肿瘤能力的丧失和特异性的缺乏而受限。在此,我们综述了当前通过基因工程赋予NK细胞增强的肿瘤杀伤能力和特异性的方法。提高对细胞因子的敏感性以及保护NK细胞免受免疫检查点抑制,赋予了NK细胞在肿瘤微环境中的持久性。在NK细胞中转导嵌合抗原受体(CAR)在临床前模型中成功靶向了血液系统肿瘤和实体瘤。利用人类多能干细胞作为可扩增且易于基因操作的平台,为癌症免疫治疗提供了稳定的工程化NK细胞来源。我们强调,来自人类多能干细胞的多能干细胞来源的CAR-NK细胞是一种有前景的癌症免疫治疗方法。
The use of natural killer (NK) cells in cancer immunotherapy demonstrates promising potential, yet its efficacy is often limited due to the loss of tumor-killing capacity and lack of specificity in vivo.
Here, we review current approaches to confer enhanced tumor-killing capacity and specificity by genetic engineering. Increasing sensitivity to cytokines and protecting NK cells from the immune checkpoint endowed sustainability of NK cells in the tumor microenvironment.
Transducing chimeric antigen receptor (CAR) in NK cells successfully targeted both hematologic and solid tumors in preclinical models. The use of human pluripotent stem cells as an expandable and genetically amenable platform offers a stable source of engineered NK cells for cancer immunotherapy.
We highlight that CAR-NK cells from human pluripotent stem cells are a promising approach for cancer immunotherapy.
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