AUTHOR=Ran Li-Feng , Xie Xun-Peng , Xia Ji-Zhu , Xie Fang-Lin , Fan Yan-Min , Wu Feng 

TITLE=T-lymphocytes from focused ultrasound ablation subsequently mediate cellular antitumor immunity after adoptive cell transfer immunotherapy

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1155229

DOI=10.3389/fimmu.2023.1155229

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Our previous studies found that high-intensity focused ultrasound (HIFU) stimulated tumor-specific T cells in a mouse H<sub>22</sub> 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.</p></sec><sec><title>Methods</title><p>Sixty H<sub>22</sub> 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<sup>6</sup> T cells from HIFU treated-mice were intravenously injected into each syngeneic H<sub>22</sub> tumor-bearing mouse twice on day 3 and 4, followed by the sacrifice for immunological assessments at 14 days after the adoptive transfer.</p></sec><sec><title>Results</title><p>T cells from HIFU-treated mice could significantly enhance the cytotoxicity of CTLs (<italic>p</italic> &lt; 0.001), with a significant increase of TNF-α (<italic>p</italic> &lt; 0.001) and IFN-γ secretion (<italic>p</italic> &lt; 0.001). Compared to control and sham-HIFU groups, the number of Fas ligand<sup>+</sup> and perforin<sup>+</sup> tumor-infiltrating lymphocytes (TILs) and apoptotic H<sub>22</sub> tumor cells were significantly higher (<italic>p</italic> &lt; 0.001) in the HIFU group. There were linear correlations between apoptotic tumor cells and Fas ligand<sup>+</sup> TILs (r = 0.9145, p &lt; 0.001) and perforin<sup>+</sup> TILs (r = 0.9619, p &lt; 0.001).</p></sec><sec><title>Conclusion</title><p>T cells from HIFU-treated mice can subsequently mediate cellular antitumor immunity, which may play an important role in the HIFU-based immunomodulation.</p></sec>