Low-pressure pulsed focused ultrasound with microbubbles promotes an anticancer immunological response

J Transl Med. 2012 Nov 11;10:221. doi: 10.1186/1479-5876-10-221.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Computer Systems
  • Disease Progression
  • Flow Cytometry
  • Humans
  • Immunity / immunology
  • Mice
  • Mice, Inbred BALB C
  • Microbubbles / therapeutic use*
  • Microscopy, Fluorescence
  • Microvessels / pathology
  • Models, Immunological
  • Neoplasms / blood supply
  • Neoplasms / diagnostic imaging*
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Permeability
  • Pressure*
  • Temperature
  • Tumor Microenvironment / immunology
  • Ultrasonics*
  • Ultrasonography