Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan.
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan; School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
J Control Release. 2020 Jul 10;323:12-23. doi: 10.1016/j.jconrel.2020.04.023. Epub 2020 Apr 14.
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.
免疫疗法通过激活宿主自身的免疫系统具有消除癌症的巨大潜力，而超声的热和机械效应在肿瘤治疗中有多种应用。热疗、消融、组织粉碎和微泡稳定/惯性空化可以改变肿瘤微环境，增强免疫激活以抑制肿瘤生长。微泡空化可以增加血管通透性，从而提高免疫细胞、细胞因子、抗原和抗体向肿瘤的输送。剧烈的微泡空化可以破坏肿瘤细胞，并有效地使其暴露于众多抗原，从而促进抗原呈递细胞的成熟和随后的适应性免疫细胞激活。本文综述了外周和脑肿瘤治疗，甚至退行性脑疾病治疗中超声诱导免疫调节的机制，并比较了它们。通过利用载药微泡的空化来逆转肿瘤至免疫活性微环境的可能性也被提出作为免疫治疗的另一种潜在途径。最后，我们讨论了超声免疫治疗未来发展的挑战和机遇。
