Immunological effect of irreversible electroporation on hepatocellular carcinoma.

Immunological effect of irreversible electroporation on hepatocellular carcinoma.
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DOI:
10.1186/s12885-021-08176-x
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发表时间:
2021-04-21
期刊:
影响因子:
3.8
通讯作者:
Wu Z
Wu Z
中科院分区:
医学2区
文献类型:
--
作者:
Guo X;Du F;Liu Q;Guo Y;Wang Q;Huang W;Wang Z;Ding X;Wu Z

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本研究旨在探讨不可逆电穿孔(IRE)消融肿瘤的免疫学效应。我们评估了肝细胞癌(HCC)患者接受IRE治疗后的全身免疫应答。同时检测IRE组和对照组荷瘤小鼠肿瘤浸润T淋巴细胞和血清细胞因子水平。我们观察到,IRE诱导白细胞,中性粒细胞和单核细胞计数增加,淋巴细胞计数减少,1天后IRE和7天内恢复到基线值的患者。同时,循环中的CD 4 + T细胞亚群在IRE后1天下降,但CD 8 + T细胞亚群没有下降。活化T细胞和自然杀伤(NK)细胞增加,调节性T(Treg)细胞减少。此外,在小鼠的消融性肿瘤上观察到细胞毒性CD 8 + T细胞浸润的显著增加。IRE组血清IFN-γ水平明显升高。我们的研究表明,IRE上调患者外周血中活化的T细胞,下调TcR。同时,动物模型的结果表明,IRE可诱导以细胞毒性CD 8 + T细胞浸润为主的抗肿瘤适应性免疫,并伴有TcR降低。
This study intends to investigate the immunological effects of tumor ablation with irreversible electroporation (IRE). We evaluated the systemic immune response in patients with hepatocellular carcinoma (HCC) after IRE treatment. Furthermore, we analyzed the tumor infiltrating T lymphocytes and the level of serum cytokines in IRE and control groups of tumor-bearing mice. We observed that IRE induced an increase in WBC, neutrophil and monocyte counts and a decrease in lymphocyte count 1 day post-IRE and returned to baseline values within 7 days in the patients. Meanwhile, circulating CD4+ T cell subsets, but not CD8+, decreased 1 day post-IRE. The activated T cells and natural killer (NK) cells increased, and regulatory T (Treg) cells decreased. Furthermore, a significant increase in cytotoxic CD8+ T cells infiltration was observed on ablative tumors in mice. The level of serum IFN-γ also significantly increased in the IRE group. Our study demonstrated that IRE upregulated activated T cells and downregulated Tregs in the peripheral blood of patients. Meanwhile, the results from the animal model indicated that IRE could induce antitumor adaptive immunity dominated by the infiltration of cytotoxic CD8+ T cells into the tumors, accompanied by reduced Tregs.
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