Mechanical Vibration-Induced Change in Stiffness of Breast Cancer Cells Promotes Natural Killer Cell-Mediated Tumor Killing Activity

Although natural killer (NK) cells are key players in the immune response against tumors, their performance is restricted when it comes to solid cancers like triple-negative breast cancer (TNBC). This study proposes an NK cell-mediated immunotherapy strategy that enhances NK cytotoxicity by modulating the stiffness of TNBC cells through mechanical vibration. Using an in vitro model with MDA-MB-231 cells, a vibration culture system (1.0 g at 50 Hz, 1 min stimulus/1 min rest for 1 h) was applied to increase cell stiffness. Cytotoxicity assays revealed a 2.45-fold increase in NK cell-mediated killing of stiffened MDA-MB-231 cells compared to controls. Immunofluorescence, RT-qPCR, and calcium flux assays demonstrated enhanced NK cell activation, including improved target recognition, mechanosensitive ion channel activation, calcium influx, lytic granule release, and cytokine responses. These findings suggest that mechanical vibration-induced tumor cell stiffening is a promising, noninvasive strategy to improve NK cell function and enhance tumor immunotherapy.