Cellular mechanoactivation of antigen-presenting cells and T cells for cancer immunotherapy

Cells convert mechanical stimuli into biochemical signals through mechanotransduction, a process that has emerged as a promising approach in cancer immunotherapy. Mechanical forces alter extracellular protein conformation, particularly mechanosensitive ion channels, leading to Ca 2+ influx and subsequent cascades of events that modulate cellular function and behavior. Recent discoveries indicate the potential of mechanotransduction as a novel approach for enhancing immune cell activation in cancer treatment modalities. Antigen-presenting cells (APCs) and T cells have become the focus of novel approaches to combat cancer. While current clinical ex vivo methods for APC activation often demonstrate limited efficiency, mechanotransduction techniques demonstrate remarkable potential for dramatically enhancing APC activation, potentially leading to improved therapeutic outcomes. Researchers have explored the mechanosensitivity of T cells to enhance CAR T therapy's specificity and controllability. Additionally, scientists have mechanically activated cancer cells engineered to express priming antigens, which are critical for synthetic Notch (SynNotch) CAR T cell therapy. Among the various mechanotransduction stimuli, fluid shear stress (FSS) and ultrasound have emerged as new and effective approaches for immune cell activation. This article reviews the latest discoveries in the mechanoactivation of APCs, T cells, and engineered CAR T cells utilizing FSS and ultrasound. • Immune cells respond to various forms of mechanical force, such as that produced by fluid shear stress or focused ultrasound. • Mechanosensitive ion channels, such as Piezo1, allow calcium influx and affect intracellular signal transduction processes. • This article describes clinically practical applications of immune mechanoactivation and future research directions.