Clinical HIFU Center for Tumor Therapy, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Institute of Ultrasonic Engineering in Medicine, Chongqing Medical University, Chongqing, China.
Front Immunol. 2023 Jul 26;14:1155229. doi: 10.3389/fimmu.2023.1155229. eCollection 2023.
Our previous studies found that high-intensity focused ultrasound (HIFU) stimulated tumor-specific T cells in a mouse H 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 H 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 T cells from HIFU treated-mice were intravenously injected into each syngeneic H 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 ( < 0.001), with a significant increase of TNF-α ( < 0.001) and IFN-γ secretion ( < 0.001). Compared to control and sham-HIFU groups, the number of Fas ligand and perforin tumor-infiltrating lymphocytes (TILs) and apoptotic H tumor cells were significantly higher ( < 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.
我们之前的研究发现，高强度聚焦超声（HIFU）在小鼠 H 肿瘤模型中刺激肿瘤特异性 T 细胞，从 HIFU 治疗的小鼠中过继转移 T 细胞可以随后更强地抑制植入肿瘤的生长和进展。本研究旨在探讨聚焦超声消融在 HIFU 介导免疫调节中 T 细胞的作用机制。
60 只 H 肿瘤荷瘤小鼠分别接受 HIFU 或假 HIFU 治疗，30 只同基因 naive 小鼠作为对照。各组小鼠均在 HIFU 后第 14 天处死，获得脾 T 细胞悬液。采用过继细胞转移模型，将 1×10 T 细胞从 HIFU 治疗的小鼠中两次静脉注射到每只同基因 H 肿瘤荷瘤小鼠中，分别在第 3 天和第 4 天，在过继转移后 14 天处死进行免疫评估。
来自 HIFU 治疗的小鼠的 T 细胞可显著增强 CTLs 的细胞毒性（<0.001），TNF-α（<0.001）和 IFN-γ分泌显著增加（<0.001）。与对照组和假 HIFU 组相比，HIFU 组 Fas 配体和穿孔素肿瘤浸润淋巴细胞（TILs）和凋亡 H 肿瘤细胞的数量显著增加（<0.001）。凋亡肿瘤细胞与 Fas 配体 TILs（r=0.9145，p<0.001）和穿孔素 TILs（r=0.9619，p<0.001）之间存在线性相关性。
来自 HIFU 治疗的小鼠的 T 细胞可以随后介导细胞抗肿瘤免疫，这可能在 HIFU 为基础的免疫调节中发挥重要作用。
