CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:T-lymphocytes from focused ultrasound ablation subsequently mediate cellular antitumor immunity after adoptive cell transfer immunotherapy.
T-lymphocytes from focused ultrasound ablation subsequently mediate cellular antitumor immunity after adoptive cell transfer immunotherapy.
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来自 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 的免疫调节中发挥重要作用。
我们先前的研究发现,高强度聚焦超声(HIFU)在小鼠H22肿瘤模型中刺激了肿瘤特异性T细胞,并且从HIFU处理小鼠中过继转移的T细胞随后能够对植入肿瘤的生长和进展产生更强的抑制作用。本研究旨在探讨聚焦超声消融中T细胞在HIFU介导的免疫调节中的机制。
60只H 22荷瘤小鼠分别接受HIFU或假HIFU治疗,30只未致敏的同系小鼠作为对照。所有小鼠在HIFU后第14天安乐死,并获取各组脾T细胞悬液。采用过继细胞转移模型,将来自HIFU治疗小鼠的总计1 × 10 6个T细胞在第3天和第4天两次静脉注射至每只同系H 22荷瘤小鼠,随后在过继转移后14天处死以进行免疫学评估。
来自HIFU处理小鼠的T细胞能显著增强CTLs的细胞毒性(p < 0.001),同时TNF-α(p < 0.001)和IFN-γ分泌(p < 0.001)显著增加。与对照组和假HIFU组相比,HIFU组中Fas配体+和穿孔素+TIL(肿瘤浸润淋巴细胞)(TILs)以及凋亡H 22肿瘤细胞的数量显著更高(p < 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。
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.
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.
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).
T cells from HIFU-treated mice can subsequently mediate cellular antitumor immunity, which may play an important role in the HIFU-based immunomodulation.
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