Ultrasound in tumor immunotherapy: Current status and future developments

Immunotherapy has considerable potential in eliminating cancers by activating the host's own immune system, while the thermal and mechanical effects of ultrasound have various applications in tumor therapy. Hyperthermia, ablation, histotripsy, and microbubble stable/inertial cavitation can alter the tumor microenvironment to enhance immunoactivation to inhibit tumor growth. Microbubble cavitation can increase vessel permeability and thereby improve the delivery of immune cells, cytokines, antigens, and antibodies to tumors. Violent microbubble cavitation can disrupt tumor cells and efficiently expose them to numerous antigens so as to promote the maturity of antigen-presenting cells and subsequent adaptive immune-cell activation. This review provides an overview and compares the mechanisms of ultrasound-induced immune modulation for peripheral and brain tumor therapy, even degenerative brain diseases therapy. The possibility of reversing tumors to an immunoactive microenvironment by utilizing the cavitation of microbubbles loaded with therapeutic gases is also proposed as another potential pathway for immunotherapy. Finally, we disuss the challenges and opportunities of ultrasound in immunotherapy for future development.