Huse Morgan
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nat Rev Immunol. 2025 May 1. doi: 10.1038/s41577-025-01173-2.
Cytotoxic lymphocytes counter intracellular pathogens and cancer by recognizing and destroying infected or transformed target cells. The basis for their function is the cytolytic immune synapse, a structurally stereotyped cell-cell interface through which lymphocytes deliver toxic proteins to target cells. The immune synapse is a highly dynamic contact capable of exerting nanonewton-scale forces against the target cell. In recent years, it has become clear that the interplay between these forces and the biophysical properties of the target influences the entirety of the cytotoxic response, from the initial activation of cytotoxic lymphocytes to the release of dying target cells. As a result, cellular cytotoxicity has become an exemplar of the ways in which biomechanics can regulate immune cell activation and effector function. This Review covers recent progress in this area, which has prompted a reconsideration of target cell killing from a more mechanobiological perspective.
细胞毒性淋巴细胞通过识别并摧毁被感染或转化的靶细胞来对抗细胞内病原体和癌症。它们发挥功能的基础是溶细胞免疫突触，这是一种结构固定的细胞间界面，淋巴细胞通过它将毒性蛋白传递给靶细胞。免疫突触是一种高度动态的接触，能够对靶细胞施加纳牛顿级别的力。近年来，很明显这些力与靶细胞的生物物理特性之间的相互作用会影响整个细胞毒性反应，从细胞毒性淋巴细胞的初始激活到垂死靶细胞的释放。因此，细胞毒性已成为生物力学调节免疫细胞激活和效应功能方式的一个范例。本综述涵盖了该领域的最新进展，这促使人们从更机械生物学的角度重新审视靶细胞杀伤问题。
