Immunoresistant to immunosensitive - Histotripsy's unique potential to overcome resistance.

Histotripsy is a novel, non-thermal ultrasound-based technology that utilizes focused acoustic waves to mechanically destroy tumor tissue. This review examines histotripsy's potential to overcome immunoresistance and treat metastatic cancers by inducing potent innate and adaptive anti-tumor immune responses. Tumor destruction releases tumor-specific antigens and damage-associated molecular patterns, facilitating immune activation and transforming the tumor microenvironment from immunologically "cold" to "hot". Preclinical studies show increased CD8 + T cell infiltration, macrophage repolarization towards a pro-inflammatory phenotype, and both local and distant (abscopal) tumor regression. Clinically, patient trials in hepatic tumors report high procedural success and safety, with initial reports of abscopal responses suggesting significant potential systemic benefit. Histotripsy offers potential benefits over radiation therapy, which rarely induces a systemic response, and immune checkpoint inhibitors, which are associated with severe systemic adverse effects. Although further clinical validation is needed, accumulating evidence positions histotripsy as a promising advancement in minimally invasive, immunomodulatory cancer treatment.