Focused ultrasound: tumour ablation and its potential to enhance immunological therapy to cancer

Abstract

Various kinds of image-guided techniques have been successfully applied in the last years for the treatment of tumours, as alternative to surgical resection. High intensity focused ultrasound (HIFU) is a novel, totally non-invasive, image-guided technique that allows for achieving tissue destruction with the application of focused ultrasound at high intensity. This technique has been successfully applied for the treatment of a large variety of diseases, including oncological and non-oncological diseases. One of the most fascinating aspects of image-guided ablations, and particularly of HIFU, is the reported possibility of determining a sort of stimulation of the immune system, with an unexpected "systemic" response to treatments designed to be "local". In the present article the mechanisms of action of HIFU are described, and the main clinical applications of this technique are reported, with a particular focus on the immune-stimulation process that might originate from tumour ablations.

Focused ultrasound stimulates ER localized mechanosensitive PANNEXIN-1 to mediate intracellular calcium release in invasive cancer cells

“…At high intensities, FUS has been used clinically to thermally ablate tumor cells (FUS and Cancer Immunotherapy, Workshop, 2019). Perhaps more importantly at lower intensities FUS has been shown to stimulate an inflammatory response cancer models which can boost the efficacy of immunotherapy (Bonaventura et al, 2019;Curley et al, 2017;Li et al, 2018;Mauri et al, 2018). Low-intensity FUS, has not yet used in cancer therapy, partly due to our limited understanding of its effects and mechanism of action.…”

“…Classically immunologically "cold" cancers include glioblastomas, ovarian, prostate, pancreatic, and most breast cancers, all extremely resistant to current therapies. FUS can be potentially be used as an adjunct therapy to induce secretion of cytokines/chemokines from 'cold' cancer cells and mediate conversion into a 'hot' tumor responsive to immunotherapy (Curley et al, 2017;Mauri et al, 2018). Of course, more work will be required in a well-controlled cellular model to understand the critical signaling pathways/ molecules and mechanisms necessary for successful clinical translation of this technology.…”

“…High-intensity (>5 W/cm 2 ) continuous FUS generates a systemic immune stimulatory effect resulting in tumor ablation (Lu et al, 2009). Pulsed FUS (i.e., non-continuous stimulus to minimize heat generation) (Hersh et al, 2016) may induce a more refined cellular/molecular immune response, (Ziadloo et al, 2012) by initiating inflammatory responses which boost cancer immunotherapy (Curley et al, 2017;Mauri et al, 2018). FUS may thus offer a new approach to overcome cancer immune-resistance, a well-known limitation preventing more wide-spread clinical adoption of successful immunotherapies such as CAR T cells (Caliendo et al, 2019;Tokarew et al, 2019).…”

Applications of Focused Ultrasound in Cerebrovascular Diseases and Brain Tumors

“…Numerous clinical and preclinical studies have demonstrated the possibility to influence immune response against cancer. It has to be said that all the immunomodulation has been described on other tumors and has not been validated in brain tumors [72,73]. The mechanism behind immunomodulation is complex and is related to all the FUS effects ( Fig.…”

Ultrasound-mediated microbubble destruction: a new method in cancer immunotherapy

“…Stable cavitation refers to the oscillation phenomenon in which a microbubble dilates at its syntonous size, creating a liquid flow called microstreams around the microbubbles. When these oscillating microbubbles reach cells, shear stress is generated, enhancing the permeability of the cell membrane 21,22…”