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聚焦超声消融后的 T 淋巴细胞在过继性细胞转移免疫治疗后介导细胞抗肿瘤免疫

英文原题:T-lymphocytes from focused ultrasound ablation subsequently mediate cellular antitumor immunity after adoptive cell transfer immunotherapy.

查看英文原题

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

PubMed 2023/07/26(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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研究概要

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。

研究思路结论见上方概要

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。

展开英文摘要原文

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.

论文信息

作者
Ran LF、Xie XP、Xia JZ、Xie FL、Fan YM、Wu F
第一作者单位
Clinical HIFU Center for Tumor Therapy, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.China
通讯作者单位
Institute of Ultrasonic Engineering in Medicine, Chongqing Medical University, Chongqing, China.China
文献类型
非美国政府资助研究
期刊
Frontiers in immunology2023
原文标识
PubMed 37564660 · DOI 10.3389/fimmu.2023.1155229