Cell softness renders cytotoxic T lymphocytes and T leukemic cells resistant to perforin-mediated killing

• DOI: 10.1038/s41467-024-45750-w
• Publication Date: 2024-02-15T16:02:41Z
• Authors: Yabo Zhou; Dianheng Wang; Li Zhou; Nannan Zhou; Zhenfeng Wang; Jie Chen; Ruiyang Pang; Haixia Fu; Qiusha Huang; Fang Dong; Hui Cheng; Huafeng Zhang; Ke Tang; Jingwei Ma; Jiadi Lv; Tao Cheng; Roland Fiskesund; Xiaohui Zhang; Bo Huang
• Keywords: CTL*

Abstract Mechanical force contributes to perforin pore formation at immune synapses, thus facilitating the cytotoxic T lymphocytes (CTL)-mediated killing of tumor cells in a unidirectional fashion. How such mechanical cues affect CTL evasion perforin-mediated autolysis remains unclear. Here we show that activated CTLs use their softness evade autolysis, which, however, is shared by leukemic killing. Downregulation filamin A identified induce via ZAP70-mediated YAP Y357 phosphorylation and activation. Despite requirements both cell types for induction, are more resistant inhibitors than malignant cells, potentially due higher expression drug-resistant transporter, MDR1, CTLs. As result, moderate inhibition stiffens but spares CTLs, allowing cytolyze without autolysis. Our findings hint force-based immunotherapeutic strategy against leukemia.