Cavitation bubble-assisted high-intensity focused ultrasound induces abscopal immune responses

Cancer treatments are often associated with limitations such as invasiveness, harmful side effects, and limited success in distant metastases. High-intensity focused ultrasound (HIFU) presents a noninvasive method for destroying tumors; nonetheless, its use is mainly confined to localized cases. In this study, we applied a novel HIFU technology, termed Trigger HIFU sequence (“Trigger HIFU”), which not only effectively curtailed growth at the site of treatment, but also prevented tumor advancement in remote, untreated areas through immune-mediated abscopal effects. Using a mouse model with bilateral MC38 colon carcinoma, applying Trigger HIFU to tumors on the right flank caused a significant reduction in the growth of treated and untreated tumors on the left flank. The treated tumors underwent approximately a 75 % decrease in volume compared with the controls. Flow cytometry showed a notable increase in tumor-infiltrating CD8⁺cytotoxic T and CD11c⁺dendritic cells in both the treated and untreated tumors. However, CD8⁺T cell depletion eliminated the anti-tumor effects locally and at distant sites. Mechanistically, Trigger HIFU induces immunogenic cell death, characterized by apoptosis and the release of damage-associated molecular patterns, such as adenosine triphosphate and high mobility group box 1 protein. Moreover, combining Trigger HIFU with anti-programmed death-1 checkpoint inhibition enhances therapeutic efficacy beyond that of either treatment alone, indicating potential synergistic clinical applications. These findings extend beyond conventional HIFU by demonstrating systemic antitumor immune activation, thereby offering new possibilities for the treatment of metastatic disease through local intervention.