Figure 2.

Schematic depiction of selected mechanisms underlying the anti-tumor effects of non-invasive energy deposition via focused ultrasound (FUS). These mechanisms are not mutually exclusive, and indeed, co-exist on a continuum; however, FUS treatment protocols can be adjusted to maximize some mechanisms and minimize others. Most commonly, this involves minimizing heat generation relative to cavitation and radiation forces. This figure is adapted with significant revision froma review by Victor Frenkel, [102], where the reader will find a more comprehensive discussion of these mechanisms as they relate to localized delivery of therapeutics to solid tumors, beyond the immuno-adjuvant effects reviewed here. *Immunogenic cellular membrane protein modulation has also been observed with lowintensity/minimal-thermal protocols. †Acute T-helper (Th)1-type inflammatory responses have also been observed with thermal-emphasis protocols. ‡Disruption of the extracellularmatrix (ECM) / tumor stroma is likely the sequela of both radiative forces and acoustic cavitation activity. See text and Table 1 for details.