High-intensity focused ultrasound tumor ablation activates autologous tumor-specific cytotoxic T lymphocytes

Ultrasound Med Biol. 2012 Aug;38(8):1363-71. doi: 10.1016/j.ultrasmedbio.2012.03.009. Epub 2012 May 24.


Previous studies have shown that high-intensity focused ultrasound (HIFU) ablation can enhance host antitumor immune response, though the mechanism is still unknown. In the present study, we investigated whether HIFU ablation could activate tumor-specific T lymphocytes and then induce antitumor cellular immunity. We studied 70 C57BL/6J mice bearing the H(22) tumor; they were randomly divided into a HIFU group and a sham-HIFU group. Of the mice, 35 in the HIFU group underwent HIFU ablation of the H(22) hepatic tumor, and the remaining 35 received a sham-HIFU procedure. In addition, 35 female, naïve syngeneic C57BL/6J mice were used as controls. All mice were sacrificed 14 days after HIFU, and the spleens were harvested. The function of T lymphocytes was determined. As a valuable tool for detecting and characterizing peptide-specific cells, the frequency of MHC class I tetramer/CD8-positive cells was quantified, which could help to determine the response and number of T lymphocytes. The therapeutic effect of the HIFU-activated lymphocytes on tumor-bearing mice was investigated after adoptive transfer of the lymphocytes. The results showed that compared to sham-HIFU and control groups, HIFU ablation significantly increased the cytotoxicity of cytotoxic T lymphocytes (p < 0.05), with a significant increase of IFN-γ and TNF-α secretion (p < 0.001). The frequency of the MHC class I tetramer/CD8-positive cells was significantly higher in the HIFU group (p < 0.05). A stronger inhibition of tumor progression and higher survival rates were observed to be significant after adoptive immunotherapy in the HIFU group as compared to the sham-HIFU and control groups (p < 0.01). It is concluded that HIFU ablation could activate tumor-specific T lymphocytes, thus inducing antitumor cellular immune responses in tumor-bearing mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / therapy*
  • Cell Line, Tumor
  • Female
  • High-Energy Shock Waves
  • High-Intensity Focused Ultrasound Ablation / methods
  • Liver Neoplasms, Experimental / immunology*
  • Liver Neoplasms, Experimental / therapy*
  • Lymphocyte Activation / immunology*
  • Lymphocyte Activation / radiation effects
  • Mice
  • Mice, Inbred C57BL
  • Random Allocation
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / radiation effects
  • Treatment Outcome