Irreversible electroporation induces CD8+ T cell immune response against post-ablation hepatocellular carcinoma growth
Irreversible electroporation induces CD8+ T cell immune response against post-ablation hepatocellular carcinoma growth
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不可逆电穿孔诱导 CD8( ) T 细胞免疫反应对抗消融后肝细胞癌生长
DOI：
10.1016/j.canlet.2021.01.001
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发表时间：
2021-01-23
期刊：
影响因子：
9.7
通讯作者：
Kuang, Ming
中科院分区：
文献类型：
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作者：
Dai, Zihao;Wang, Zongren;Kuang, Ming
消融治疗引起抗肿瘤免疫，但对肝细胞癌（HCC）中出现的不可逆电穿孔（IRE）诱导的免疫的认识有限。为了研究IRE诱导的免疫效应及其在预防消融后HCC进展中的作用，采用皮下H22肝癌的C57 BL/6 J小鼠模型。IRE治疗显著抑制HCC生长，治疗小鼠在二次肿瘤注射后无肿瘤，并显示脾干扰素-γ（IFN-γ）+CD 8（+）T细胞增加。此外，在第7天IRE后，更多的CD 8（+）T和树突状细胞（而不是CD 4（+）T、B或NK细胞）浸润到消融周围区域。IRE后CD 8（+）T细胞的耗竭诱导局部肿瘤再生长和远处转移。使用IRE处理的H22裂解物的疫苗接种预防小鼠中的肿瘤发生，表明保护性免疫应答。IRE还通过减少局部和脾脏Treg和PD-1（+）T细胞来减轻免疫抑制。关于机制，IRE诱导细胞坏死和显著释放与CD 8（+）T细胞免疫关键的ATP、高迁移率族蛋白1和钙网蛋白等CD 8（+）T细胞相关分子模式。总之，IRE是一种很有前途的方法，可以唤起CD 8（+）T细胞免疫，有助于预防消融后HCC的进展。
Ablative treatment evokes antitumor immunity, but knowledge on the emerging irreversible electroporation (IRE)-induced immunity in hepatocellular carcinoma (HCC) is limited. To investigate the immune effects induced by IRE and its role in preventing post-ablation HCC progression, a C57BL/6J mouse model bearing subcutaneous H22 hepatoma was employed. IRE treatment significantly suppresses HCC growth, and treated mice are tumor-free after secondary tumor injection and show increased splenic interferon-gamma (IFN-gamma)+CD8(+) T cells. Additionally, more CD8(+) T and dendritic cells, but not CD4(+) T, B or NK cells, infiltrate into peri-ablation zones after IRE at day 7. Depletion of CD8(+) T cells induces local tumor regrowth and distant metastasis after IRE. Vaccination using IRE-processed H22 lysates prevents tumorigenesis in mice, suggesting a protective immune response. IRE also alleviates immunosuppression by reducing local and splenic Treg and PD-1(+) T cells. Regarding mechanism, IRE induces cell necrosis and significant release of danger-associated molecular patterns including ATP, high mobility group box 1 and calreticulin that are pivotal to CD8(+) T cell immunity. Together, IRE is a promising approach to evoke CD8(+) T cell immunity, which help prevent post-ablation HCC progression.