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:Intracellular checkpoints for NK cell cancer immunotherapy.
Intracellular checkpoints for NK cell cancer immunotherapy.
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自然杀伤(NK)细胞是先天免疫中的重要淋巴细胞,在抗肿瘤过程中发挥关键作用。然而,肿瘤浸润 NK 细胞常处于功能低下或耗竭状态。一方面,这种状态与抑制性 NK 细胞检查点受体及其配体之间依赖具体情境的相互作用有关;这些相互作用通常随肿瘤类型及肿瘤进展阶段而异。另一方面,NK 细胞内检查点分子的抑制作用在不同肿瘤类型间更为相似,构成限制 NK 细胞治疗潜力的共同机制。本综述回顾了参与 NK 细胞生物学不同环节的代表性细胞内检查点分子,并讨论靶向这些分子以促进抗肿瘤 NK 细胞治疗的潜力。
Natural killer (NK) cells are key innate immune lymphocytes, which play important roles against tumors.
However, tumor-infiltrating NK cells are always hypofunctional/exhaustive. On the one hand, this state is contributed by context-dependent interactions between inhibitory NK cell checkpoint receptors and their ligands, which usually vary in different tumor types and stages during tumor development.
On the other hand, the inhibitory functions of intracellular checkpoint molecules of NK cells are more similar across different tumor types, representing common mechanisms limiting the potential of NK cell therapy. In this review, representative NK cell intracellular checkpoint molecules in different aspects of NK cell biology were reviewed, and therapeutic potentials were discussed by targeting these molecules to promote antitumor NK cell therapy.
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