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NK 细胞的力学生物学——迫使 NK 感知靶细胞

英文原题:The mechanobiology of NK cells- 'Forcing NK to Sense' target cells.

查看英文原题

The mechanobiology of NK cells- 'Forcing NK to Sense' target cells.

PubMed 2023/02/13(内容时间) Biochim Biophys Acta Rev Cancer Q1 · IF 11.2(JCR 2025)

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中文摘要

自然杀伤(NK)细胞是固有免疫淋巴细胞,能够识别并杀伤肿瘤细胞和感染细胞,这使其成为新一代免疫治疗中独特的“即用型”候选细胞。在稳态和病理生理状态下,生物力学力为NK免疫应答增添了额外的免疫调控。事实上,细胞和组织生物力学影响NK受体聚集、细胞骨架重塑、NK穿越内皮细胞的迁移、核力学,甚至NK与树突状细胞的相互作用,为NK免疫治疗提供了大量尚未探索但重要的动态调控。人类NK细胞的异质性使这些事件更加复杂。一个重要问题仍然存在:生化和生物力学线索是否以及如何协同参与NK细胞力转导——即机械力被感知、转导并转化为下游力学和生化信号的过程。本文中,我们综述了在理解NK细胞如何感知和力转导生物物理线索方面的最新进展。我们重点关注细胞骨架交互调控如何调节NK细胞功能,同时兼顾NK细胞的异质性、NK抗肿瘤活性的直接和间接力学线索,最后关注在系统层面上与NK细胞生物学具有转化相关性的工程学进展。

展开英文摘要原文

Natural killer (NK) cells are innate immune lymphocytes that recognize and kill cancer and infected cells, which makes them unique 'off-the-shelf' candidates for a new generation of immunotherapies. Biomechanical forces in homeostasis and pathophysiology accrue additional immune regulation for NK immune responses. Indeed, cellular and tissue biomechanics impact NK receptor clustering, cytoskeleton remodeling, NK transmigration through endothelial cells, nuclear mechanics, and even NK-dendritic cell interaction, offering a plethora of unexplored yet important dynamic regulation for NK immunotherapy.

Such events are made more complex by the heterogeneity of human NK cells. A significant question remains on whether and how biochemical and biomechanical cues collaborate for NK cell mechanotransduction, a process whereby mechanical force is sensed, transduced, and translated to downstream mechanical and biochemical signalling.

Herein, we review recent advances in understanding how NK cells perceive and mechanotransduce biophysical cues.

We focus on how the cellular cytoskeleton crosstalk regulates NK cell function while bearing in mind the heterogeneity of NK cells, the direct and indirect mechanical cues for NK anti-tumor activity, and finally, engineering advances that are of translational relevance to NK cell biology at the systems level.

论文信息

作者
Wong DCP、Ding JL
第一作者单位
Department of Biological Sciences, National University of Singapore, 117543, Singapore. Electronic address: dbsdwcp@nus.edu.sg.Singapore
通讯作者单位
Department of Biological Sciences, National University of Singapore, 117543, Singapore; Integrative Sciences and Engineering Programme, National University of Singapore, 119077, Singapore. Electronic address: dbsdjl@nus.edu.sg.Singapore
文献类型
综述 · 非美国政府资助研究
期刊
Biochimica et biophysica acta. Reviews on cancer2023 Mar
原文标识
PubMed 36791921 · DOI 10.1016/j.bbcan.2023.188860