title: Low-pressure pulsed focused ultrasound with microbubbles promotes an anticancer immunological response.
abstract: BACKGROUND
  High-intensity focused-ultrasound (HIFU) has been successfully employed for thermal ablation of tumors in clinical settings. Continuous- or pulsed-mode HIFU may also induce a host antitumor immune response, mainly through expansion of antigen-presenting cells in response to increased cellular debris and through increased macrophage activation/infiltration. Here we demonstrated that another form of focused ultrasound delivery, using low-pressure, pulsed-mode exposure in the presence of microbubbles (MBs), may also trigger an antitumor immunological response and inhibit tumor growth.
  
  
  METHODS
  A total of 280 tumor-bearing animals were subjected to sonographically-guided FUS. Implanted tumors were exposed to low-pressure FUS (0.6 to 1.4 MPa) with MBs to increase the permeability of tumor microvasculature.
  
  
  RESULTS
  Tumor progression was suppressed by both 0.6 and 1.4-MPa MB-enhanced FUS exposures. We observed a transient increase in infiltration of non-T regulatory (non-Treg) tumor infiltrating lymphocytes (TILs) and continual infiltration of CD8+ cytotoxic T-lymphocytes (CTL). The ratio of CD8+/Treg increased significantly and tumor growth was inhibited.
  
  
  CONCLUSIONS
  Our findings suggest that low-pressure FUS exposure with MBs may constitute a useful tool for triggering an anticancer immune response, for potential cancer immunotherapy.
authors.affiliation: Department of Electrical Engineering, Chang-Gung University, Taoyuan, Taiwan.
authors.forename: Hao-Li
authors.initials: HL
authors.lastname: Liu
authors.forename: Han-Yi
authors.initials: HY
authors.lastname: Hsieh
authors.forename: Li-An
authors.initials: LA
authors.lastname: Lu
authors.forename: Chiao-Wen
authors.initials: CW
authors.lastname: Kang
authors.forename: Ming-Fang
authors.initials: MF
authors.lastname: Wu
authors.forename: Chun-Yen
authors.initials: CY
authors.lastname: Lin
mesh_terms: D000818:Animals; D003199:Computer Systems; D018450:Disease Progression; D005434:Flow Cytometry; D006801:Humans; D007109:Immunity / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D045423:Microbubbles / Q000627:therapeutic use*; D008856:Microscopy, Fluorescence; D055806:Microvessels / Q000473:pathology; D018448:Models, Immunological; D009369:Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000276:immunology* / Q000473:pathology; D010539:Permeability; D011312:Pressure; D013696:Temperature; D059016:Tumor Microenvironment / Q000276:immunology; D014465:Ultrasonics; D014463:Ultrasonography