自然杀伤细胞（NK细胞）是一种固有免疫淋巴细胞，能够识别和杀死癌细胞和感染细胞，这使它们成为新一代免疫治疗中独特的“现成”候选者。在稳态和病理生理学中的生物机械力对NK免疫反应累积了额外的免疫调节。实际上，细胞和组织生物力学影响NK受体聚集、细胞骨架重构、NK通过内皮细胞迁移、细胞核力学，甚至NK树突细胞相互作用，为NK免疫治疗提供了大量未被探索但重要的动态调节方式。这些事件因人类NK细胞的异质性而更加复杂。一个重要的问题仍然存在，那就是生化和生物力学提示如何协同作用于NK细胞力传导，这是一种过程，其中感知、传导和转化为下游机械和生化信号的机械力量被感知。在这里，我们回顾了最近对NK细胞如何感知和力传导生物物理信号的理解方面的进展。我们重点关注细胞骨架交互作用如何调节NK细胞功能，并意识到NK细胞的异质性、直接和间接的机械信号对NK抗肿瘤活性的影响，最后，系统层面上与NK细胞生物学有翻译相关性的工程进展。版权所有 © 2023 作者。由 Elsevier B.V. 发布。保留所有权利。

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.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.