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High-Intensity Focused Ultrasound Tumor Ablation Activates Autologous Tumor-Specific Cytotoxic T Lymphocytes

机译:高强度聚焦超声消融激活自体肿瘤特异性细胞毒性T淋巴细胞

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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, na?ve 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.
机译:先前的研究表明,高强度聚焦超声(HIFU)消融可以增强宿主的抗肿瘤免疫反应,尽管其机制仍不清楚。在本研究中,我们调查了HIFU消融是否可以激活肿瘤特异性T淋巴细胞,然后诱导抗肿瘤细胞免疫。我们研究了70只带有H 22肿瘤的C57BL / 6J小鼠。他们被随机分为HIFU组和假HIFU组。在小鼠中,HIFU组中的35例接受了H 22肝肿瘤的HIFU消融,其余35例接受了假HIFU手术。另外,将35只雌性幼稚的同系C57BL / 6J小鼠用作对照。 HIFU后14天处死所有小鼠,并收集脾脏。确定了T淋巴细胞的功能。作为检测和表征肽特异性细胞的有价值的工具,对MHC I类四聚体/ CD8阳性细胞的频率进行了定量,这可以帮助确定T淋巴细胞的应答和数量。在过继转移淋巴细胞后,研究了HIFU活化的淋巴细胞对荷瘤小鼠的治疗作用。结果表明,与假组和对照组相比,HIFU消融显着增加了细胞毒性T淋巴细胞的细胞毒性(p <0.05),同时IFN-γ和TNF-α的分泌也显着增加(p <0.001)。 HIFU组中MHC I类四聚体/ CD8阳性细胞的频率明显更高(p <0.05)。与假-HIFU组和对照组相比,HIFU组在过继免疫治疗后观察到对肿瘤进展的更强抑制和更高的存活率是显着的(p <0.01)。结论是,HIFU消融可以激活肿瘤特异性T淋巴细胞,从而在荷瘤小鼠中诱导抗肿瘤细胞免疫应答。

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