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:Targeting metabolic dysfunction of CD8 T cells and natural killer cells in cancer.
Targeting metabolic dysfunction of CD8 T cells and natural killer cells in cancer.
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代谢途径在调控免疫反应中的重要性现已得到充分确立,不同免疫细胞类型的生物能量代谢图谱绘制工作正在进行中。CD8 T细胞和自然杀伤(NK)细胞通过其细胞毒性功能以及分泌细胞因子和趋化因子,参与癌症免疫监视,在靶标识别机制上相互补充。多种免疫疗法通过刺激这些细胞类型的活性或重定向其针对肿瘤细胞的特异性来利用它们。然而,CD8 T细胞和NK细胞的抗癌活性在肿瘤微环境中迅速减弱,这与其代谢能力的下降密切相关。目前已开发出多种策略来恢复癌症免疫监视,包括靶向生物能量代谢或基因工程。本综述概述了肿瘤微环境中CD8 T细胞和NK细胞的代谢功能障碍,并重点介绍了当前旨在克服这些问题的疗法。
The importance of metabolic pathways in regulating immune responses is now well established, and a mapping of the bioenergetic metabolism of different immune cell types is under way. CD8 T cells and natural killer (NK) cells contribute to cancer immunosurveillance through their cytotoxic functions and secretion of cytokines and chemokines, complementing each other in target recognition mechanisms. Several immunotherapies leverage these cell types by either stimulating their activity or redirecting their specificity against tumour cells.
However, the anticancer activity of CD8 T cells and NK cells is rapidly diminished in the tumour microenvironment, closely linked to a decline in their metabolic capacities. Various strategies have been developed to restore cancer immunosurveillance, including targeting bioenergetic metabolism or genetic engineering. This Review provides an overview of metabolic dysfunction in CD8 T cells and NK cells within the tumour microenvironment, highlighting current therapies aiming to overcome these issues.
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