HIGH-INTENSITY FOCUSED ULTRASOUND TUMOR ABLATION ACTIVATES AUTOLOGOUS TUMOR-SPECIFIC CYTOTOXIC T LYMPHOCYTES

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, naiive 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-gamma and TNF-alpha 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. (E-mail: mfengwu@yahoo.com) (C) 2012 World Federation for Ultrasound in Medicine & Biology.