我们的前期研究发现，高强度聚焦超声（HIFU）刺激H22小鼠肿瘤特异性T细胞，在移植瘤模型中，来自HIFU处理小鼠的T细胞的移植转移后，能够更强地抑制移植瘤的生长和进展。本研究的目的是调查HIFU介导的免疫调控中，来自聚焦超声消融的T细胞机制。我们对60只H22肿瘤携带小鼠进行了HIFU或假HIFU处理，另外有30只同种小鼠作为对照。HIFU处理后的第14天，我们在每组中获取了脾T细胞悬液。通过移植细胞转移模型，我们将来自HIFU处理小鼠的总计1×106个T细胞静脉内注射进每只同种H22肿瘤携带小鼠，第3天和第4天分别注射一次，然后在移植后的第14天进行免疫评估。来自HIFU处理小鼠的T细胞能够显著增强CTLs的细胞毒性（p < 0.001），并且明显增加TNF-α的分泌（p < 0.001）和IFN-γ分泌（p < 0.001）。与对照组和假HIFU组相比，HIFU组中Fas配体+和穿孔素+的肿瘤浸润淋巴细胞（TILs）和凋亡H22肿瘤细胞的数量显著高（p < 0.001）。凋亡肿瘤细胞与Fas配体+的TILs（r = 0.9145，p < 0.001）和穿孔素+的TILs（r = 0.9619，p < 0.001）之间存在线性相关。HIFU处理小鼠的T细胞随后能够介导细胞抗肿瘤免疫，这可能在基于HIFU的免疫调控中起着重要作用。Copyright © 2023 Ran, Xie, Xia, Xie, Fan and Wu.

Our previous studies found that high-intensity focused ultrasound (HIFU) stimulated tumor-specific T cells in a mouse H22 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.Sixty H22 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 × 106 T cells from HIFU treated-mice were intravenously injected into each syngeneic H22 tumor-bearing mouse twice on day 3 and 4, followed by the sacrifice for immunological assessments at 14 days after the adoptive transfer.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 H22 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).T cells from HIFU-treated mice can subsequently mediate cellular antitumor immunity, which may play an important role in the HIFU-based immunomodulation.Copyright © 2023 Ran, Xie, Xia, Xie, Fan and Wu.