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Investigation of HIFU-induced anti-tumor immunity in a murine tumor model.

Publication ,  Journal Article
Hu, Z; Yang, XY; Liu, Y; Sankin, GN; Pua, EC; Morse, MA; Lyerly, HK; Clay, TM; Zhong, P
Published in: J Transl Med
July 11, 2007

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-gamma-secreting cells in the mice treated by focused ultrasound, with cytotoxicity induced by mechanical HIFU reaching as high as 27% at a 10:1 effector:target ratio. CONCLUSION: These studies present initial encouraging results confirming that focused ultrasound treatment can elicit a systemic anti-tumor immune response, and they suggest that this immunity is closely related to dendritic cell activation. Because DC activation was more pronounced when tumor cells were mechanically lysed by focused ultrasound treatment, mechanical HIFU in particular may be employed as a potential strategy in combination with subsequent thermal ablations for increasing the efficacy of HIFU cancer treatment by enhancing the host's anti-tumor immunity.

Duke Scholars

Published In

J Transl Med

DOI

EISSN

1479-5876

Publication Date

July 11, 2007

Volume

5

Start / End Page

34

Location

England

Related Subject Headings

  • Ultrasonography
  • Temperature
  • Neoplasms
  • Mice, Inbred C57BL
  • Mice
  • Lymph Nodes
  • Immunology
  • Immunity
  • High-Intensity Focused Ultrasound Ablation
  • Female
 

Citation

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MLA
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Hu, Z., Yang, X. Y., Liu, Y., Sankin, G. N., Pua, E. C., Morse, M. A., … Zhong, P. (2007). Investigation of HIFU-induced anti-tumor immunity in a murine tumor model. J Transl Med, 5, 34. https://doi.org/10.1186/1479-5876-5-34
Hu, Zhenlin, Xiao Yi Yang, Yunbo Liu, Georgy N. Sankin, Eric C. Pua, Michael A. Morse, H Kim Lyerly, Timothy M. Clay, and Pei Zhong. “Investigation of HIFU-induced anti-tumor immunity in a murine tumor model.J Transl Med 5 (July 11, 2007): 34. https://doi.org/10.1186/1479-5876-5-34.
Hu Z, Yang XY, Liu Y, Sankin GN, Pua EC, Morse MA, et al. Investigation of HIFU-induced anti-tumor immunity in a murine tumor model. J Transl Med. 2007 Jul 11;5:34.
Hu, Zhenlin, et al. “Investigation of HIFU-induced anti-tumor immunity in a murine tumor model.J Transl Med, vol. 5, July 2007, p. 34. Pubmed, doi:10.1186/1479-5876-5-34.
Hu Z, Yang XY, Liu Y, Sankin GN, Pua EC, Morse MA, Lyerly HK, Clay TM, Zhong P. Investigation of HIFU-induced anti-tumor immunity in a murine tumor model. J Transl Med. 2007 Jul 11;5:34.
Journal cover image

Published In

J Transl Med

DOI

EISSN

1479-5876

Publication Date

July 11, 2007

Volume

5

Start / End Page

34

Location

England

Related Subject Headings

  • Ultrasonography
  • Temperature
  • Neoplasms
  • Mice, Inbred C57BL
  • Mice
  • Lymph Nodes
  • Immunology
  • Immunity
  • High-Intensity Focused Ultrasound Ablation
  • Female