title: Thermal and mechanical high-intensity focused ultrasound: perspectives on tumor ablation, immune effects and combination strategies.
abstract: Tumor ablation technologies, such as radiofrequency-, cryo- or high-intensity focused ultrasound (HIFU) ablation will destroy tumor tissue in a minimally invasive manner. Ablation generates large volumes of tumor debris in situ, releasing multiple bio-molecules like tumor antigens and damage-associated molecular patterns. To initiate an adaptive antitumor immune response, antigen-presenting cells need to take up tumor antigens and, following activation, present them to immune effector cells. The impact of the type of tumor ablation on the precise nature, availability and suitability of the tumor debris for immune response induction, however, is poorly understood. In this review, we focus on immune effects after HIFU-mediated ablation and compare these to findings using other ablation technologies. HIFU can be used both for thermal and mechanical destruction of tissue, inducing coagulative necrosis or subcellular fragmentation, respectively. Preclinical and clinical results of HIFU tumor ablation show increased infiltration and activation of CD4+and CD8+T cells. As previously observed for other types of tumor ablation technologies, however, this ablation-induced enhanced infiltration alone appears insufficient to generate consistent protective antitumor immunity. Therapies combining ablation with immune stimulation are therefore expected to be key to boost HIFU-induced immune effects and to achieve systemic, long-lasting, antitumor immunity.
authors: Department of Tumor Immunology, Radboud University Medical Center, Geert Grooteplein 28, 6525 GA, Nijmegen, The Netherlands.
authors: Renske J E
authors: RJ
authors: van den Bijgaart
authors: Department of Tumor Immunology, Radboud University Medical Center, Geert Grooteplein 28, 6525 GA, Nijmegen, The Netherlands.
authors: Dylan C
authors: DC
authors: Eikelenboom
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Martijn
authors: M
authors: Hoogenboom
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.|MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
authors: Jurgen J
authors: JJ
authors: Fütterer
authors: Department of Tumor Immunology, Radboud University Medical Center, Geert Grooteplein 28, 6525 GA, Nijmegen, The Netherlands.
authors: Martijn H
authors: MH
authors: den Brok
authors: Department of Tumor Immunology, Radboud University Medical Center, Geert Grooteplein 28, 6525 GA, Nijmegen, The Netherlands. gosse.adema@radboudumc.nl.
authors: Gosse J
authors: GJ
authors: Adema
mesh_terms: D000818:Animals; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000601:surgery*
keywords: High-intensity focused ultrasound; Immune adjuvants; Immunotherapy; PIVAC 15; Tumor ablation