Investigation of HIFU-induced anti-tumor immunity in a murine tumor model
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BioMed Central
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Investigation of HIFU-induced anti-tumor immunity in a murine tumor model Zhenlin Hu1, Xiao Yi Yang2, Yunbo Liu1, Georgy N Sankin1, Eric C Pua1, Michael A Morse2, H Kim Lyerly2, Timothy M Clay2 and Pei Zhong*1 Address: 1Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708, USA and 2Program in Molecular Therapeutics, Departments of Surgery, Medicine, Pathology, and Immunology, and Duke Comprehensive Cancer Center, Duke University, Durham, NC 27708, USA Email: Zhenlin Hu - [email protected]; Xiao Yi Yang - [email protected]; Yunbo Liu - [email protected]; Georgy N Sankin - [email protected]; Eric C Pua - [email protected]; Michael A Morse - [email protected]; H Kim Lyerly - [email protected]; Timothy M Clay - [email protected]; Pei Zhong* - [email protected] * Corresponding author
Published: 11 July 2007 Journal of Translational Medicine 2007, 5:34
doi:10.1186/1479-5876-5-34
Received: 27 April 2007 Accepted: 11 July 2007
This article is available from: http://www.translational-medicine.com/content/5/1/34 © 2007 Hu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: High intensity focused ultrasound (HIFU) is an emerging non-invasive treatment modality for localized treatment of cancers. While current clinical strategies employ HIFU exclusively for thermal ablation of the target sites, biological responses associated with both thermal and mechanical damage from focused ultrasound have not been thoroughly investigated. In particular, endogenous danger signals from HIFU-damaged tumor cells may trigger the activation of dendritic cells. This response may play a critical role in a HIFU-elicited anti-tumor immune response which can be harnessed for more effective treatment. Methods: Mice bearing MC-38 colon adenocarcinoma tumors were treated with thermal and mechanical HIFU exposure settings in order to independently observe HIFU-induced effects on the host's immunological response. In vivo dendritic cell activity was assessed along with the host's response to challenge tumor growth. Results: Thermal and mechanical HIFU were found to increase CD11c+ cells 3.1-fold and 4-fold, respectively, as compared to 1.5-fold observed for DC injection alone. In addition, thermal and mechanical HIFU increased CFSE+ DC accumulation in draining lymph nodes 5-fold and 10-fold, respectively. Moreover, focused ultrasound treatments not only caused a reduction in the growth of primary tumors, with tumor volume decreasing by 85% for thermal HIFU and 43% for mechanical HIFU, but they also provided protection against subcutaneous tumor re-challenge. Further immunological assays confirmed an enhanced CTL activity and increased tumor-specific IFN-γ-secreting cells in the mice treated by f
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