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:Harnessing natural killer cells for cancer immunotherapy: dispatching the first responders.
Harnessing natural killer cells for cancer immunotherapy: dispatching the first responders.
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自然杀伤(NK)细胞在癌症和病毒感染的先天免疫监视中发挥关键作用。它们是“第一响应者”,能够自发识别体内的异常细胞,通过聚焦的细胞毒性机制迅速将其清除,并强效产生促炎细胞因子和趋化因子,招募并激活其他免疫细胞以启动适应性反应。从最初发现NK细胞上多样化的细胞表面受体,到表征控制其功能的调控事件,过去三十年间我们对NK细胞基础生物学的理解已显著提升。这些深入的知识揭示了日益增加的机制复杂性,为开发大量令人兴奋的新疗法打开了大门,这些疗法能够有效操控和靶向NK细胞的功能反应,尤其是在癌症患者中。在此,我们总结了调控NK细胞生物学的基本机制,综述了目前正在开发和用于刺激NK细胞反应的各种药物、细胞因子和抗体,并概述了不断演进的NK细胞过继转移治疗癌症的方法。
Natural killer (NK) cells have crucial roles in the innate immunosurveillance of cancer and viral infections. They are 'first responders' that can spontaneously recognize abnormal cells in the body, rapidly eliminate them through focused cytotoxicity mechanisms and potently produce pro-inflammatory cytokines and chemokines that recruit and activate other immune cells to initiate an adaptive response.
From the initial discovery of the diverse cell surface receptors on NK cells to the characterization of regulatory events that control their function, our understanding of the basic biology of NK cells has improved dramatically in the past three decades. This advanced knowledge has revealed increased mechanistic complexity, which has opened the doors to the development of a plethora of exciting new therapeutics that can effectively manipulate and target NK cell functional responses, particularly in cancer patients.
Here, we summarize the basic mechanisms that regulate NK cell biology, review a wide variety of drugs, cytokines and antibodies currently being developed and used to stimulate NK cell responses, and outline evolving NK cell adoptive transfer approaches to treat cancer.
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