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Open Access Research

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

Hao-Li Liu1, Han-Yi Hsieh1, Li-An Lu1, Chiao-Wen Kang2, Ming-Fang Wu3 and Chun-Yen Lin2*

Author Affiliations

1 Department of Electrical Engineering, Chang-Gung University, Taoyuan, Taiwan

2 Department of Hepatogastroenterology, Chang-Gung Memorial Hospital, Taoyuan, Taiwan

3 Animal Medicine Center, National Taiwan University, Taipei, Taiwan

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Journal of Translational Medicine 2012, 10:221  doi:10.1186/1479-5876-10-221

Published: 11 November 2012

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.