Sonoimmunology in cancer therapy: expanding crosstalk among ultrasound-materials-immune system

Sono-immunology utilizes ultrasound as a physical intervention to regulate immune cell functions and remodel the immune microenvironment through its mechanical and thermal effects, or in synergy with ultrasound-responsive materials, thereby providing visualized and quantifiable novel theories and strategies for immunotherapy of tumors and other diseases. • Mechanisms of ultrasound in reshaping immune responses are reviewed. • Living and synthetic ultrasound-responsive materials are discussed. • Strategies to enhance immune cell penetration and safety are detailed. • Sonoimmunology is explored as an emerging paradigm in oncology. Cancer immunotherapy has achieved remarkable progress, but its clinical efficacy is still limited by tumor heterogeneity and the immunosuppressive tumor microenvironment (TME). Ultrasound, as a non-invasive and highly controllable physical modality, can regulate anti-tumor immune responses by inducing immunogenic cell death, promoting antigen release, and enhancing immune cell infiltration into tumors. Moreover, recent advances in ultrasound-responsive materials, including living and synthetic systems, have provided novel strategies by enabling targeted, spatiotemporal regulation of the TME. These biocompatible materials enhance immune cell penetration, reduce systemic toxicity, and amplify anti-tumor immunity through precise modulation of immune signaling pathways. In this review, we summarize the mechanisms by which ultrasound reshapes anti-tumor immune responses, discuss the rational design of ultrasound-responsive materials to optimize immunotherapeutic efficacy, highlight their translational potential in cancer treatment, and propose the conceptual framework of sonoimmunology.