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Background: Our previous studies found that high-intensity focused ultrasound (HIFU) stimulated tumor-specific T cells in a mouse H 22 tumor model, and adoptive transfer of the T cells from HIFU-treated mice could subsequently elicit stronger inhibition on the growth and progression of the implanted tumors. The aim of this study was to investigate the mechanism of T cells from focused ultrasound ablation in HIFU-mediated immunomodulation., Methods: Sixty H 22 tumor-bearing mice were treated by either HIFU or sham-HIFU, and 30 naïve syngeneic mice served as controls. All mice were euthanized on day 14 after HIFU and splenic T cell suspensions were obtained in each group. Using an adoptive cell transfer model, a total of 1 × 10 6 T cells from HIFU treated-mice were intravenously injected into each syngeneic H 22 tumor-bearing mouse twice on day 3 and 4, followed by the sacrifice for immunological assessments at 14 days after the adoptive transfer., Results: T cells from HIFU-treated mice could significantly enhance the cytotoxicity of CTLs ( p < 0.001), with a significant increase of TNF-α ( p < 0.001) and IFN-γ secretion ( p < 0.001). Compared to control and sham-HIFU groups, the number of Fas ligand + and perforin + tumor-infiltrating lymphocytes (TILs) and apoptotic H 22 tumor cells were significantly higher ( p < 0.001) in the HIFU group. There were linear correlations between apoptotic tumor cells and Fas ligand + TILs (r = 0.9145, p < 0.001) and perforin + TILs (r = 0.9619, p < 0.001)., Conclusion: T cells from HIFU-treated mice can subsequently mediate cellular antitumor immunity, which may play an important role in the HIFU-based immunomodulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ran, Xie, Xia, Xie, Fan and Wu.)

Purpose: The aim of this study was to investigate the specific anti-tumour immunity of cytotoxic T lymphocytes (CTL) activated by high-intensity focused ultrasound (HIFU) after adoptive transfer in a murine tumour model., Materials and Methods: H22 tumour-bearing mice were treated by either HIFU or sham-HIFU, while naïve syngeneic mice were used as controls. They were sacrificed and the spleens were harvested 14 days after HIFU. T lymphocytes were obtained from the spleens, and then adoptively transferred into 40 mice each bearing a 3-day implanted H22 tumour. On day 14 after adoptive transfer, 10 mice were sacrificed in each group for assessment of the number of tumour-infiltrating T lymphocytes and interferon-gamma (IFN-γ) secreting cells. The remaining 30 mice were continuously observed for 60 days, and tumour growth, progression and survival were recorded., Results: HIFU significantly increased peripheral blood CD3(+), CD4(+) levels and CD4(+)/CD8(+) ratio (P < 0.05), CTL cytotoxicity (P < 0.01) and IFN-γ and TNF-α secretion (P < 0.01) in H22 tumour-bearing mice. Adoptive transfer of HIFU-activated T lymphocytes into the autologous tumour-bearing mice induced a significant increase of tumour-infiltrating T lymphocytes and IFN-γ-secreting cells (P < 0.001). Compared to the control and sham-HIFU groups, HIFU-activated lymphocytes elicited significant inhibition of in vivo tumour growth (P < 0.01) and progression (P < 0.0001), and longer survival time in the tumour-bearing mice (P < 0.001)., Conclusions: HIFU could enhance CTL's specific antitumour immunity. Adoptive transfer of HIFU-activated T lymphocytes could increase local antitumour immunity, and elicit stronger inhibition on tumour growth and progression, with more survival benefit in the autologous tumour-bearing mice.

The aim of this study is to investigate the efficacy and safety of extracorporeal high-intensity focused ultrasound (HIFU) in treatment of hypersplenism. Fifteen adult dogs, weighing 13-18 kg were divided into three groups: sham group, SVL group undergoing splenic vein ligation (SVL) after laparotomy, and SVL + HIFU group receiving SVL followed by extracorporeal HIFU. Pathologic and hematologic analyses were performed. We also reviewed the clinical data of 19 patients with secondary hypersplenism caused by liver cirrhosis or hepatocellular carcinoma who underwent extracorporeal HIFU. Extracorporeal HIFU significantly diminished the volume of the spleen of animals, coupled with occurrence of coagulation necrosis and fibrosis in the target area. Both platelet and red blood cell counts were significantly restored by HIFU intervention. Similarly, HIFU treatment improved the hematologic parameters in patients with hypersplenism, and no major complications were encountered. Extracorporeal HIFU intervention is effective and safe in managing secondary hypersplenism., (Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)