Low-frequency HIFU induced cancer immunotherapy: tempting challenges and potential opportunities

Immunotherapy is playing an increasingly important role in the treatment of tumors. Different from the traditional direct killing or excision therapies, immunotherapy depends on autologous immunity to kill tumor cells and tissues by activating or enhancing the body's immune system. Large numbers of recent studies suggest that low-frequency HIFU can not only enhance the intensity of the body's anti-cancer immune response, but also improve the efficiency of immunotherapy drug delivery to strengthen the effects of tumor immunotherapy. The focused ultrasound (FUS) destructs the tumor and simultaneously generates tumor debris and tumor-associated antigens, which enhances the immunogenicity of the tumor and stimulates the immune cells, inducing the body's immune response. Microbubbles are clinically used as a contrast. As a matter of fact, the addition of microbubbles can reinforce the destructive effect of FUS on the tumor and activate a stronger immune response. The combined application of ultrasound and microbubbles can more effectively open the blood brain barrier (BBB), which is beneficial to improving the intake of immune cells or immunotherapy drugs and exerting a positive influence in the lesion area. Currently, microbubbles and nanoparticles are commonly used as gene and drug carriers. Using ultrasound, the immune-related gene or antigen delivery itself can enhance the immune response and improve the efficacy of the immunotherapy.