High-frequency irreversible electroporation is an effective tumor ablation strategy that induces immunologic cell death and promotes systemic anti-tumor immunity
High-frequency irreversible electroporation is an effective tumor ablation strategy that induces immunologic cell death and promotes systemic anti-tumor immunity
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DOI：
10.1016/j.ebiom.2019.05.036
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发表时间：
2019-06-01
期刊：
影响因子：
11.1
通讯作者：
Allen, Irving C.
中科院分区：
文献类型：
--
作者：
Ringel-Scaia, Veronica M.;Beitel-White, Natalie;Allen, Irving C.
背景：尽管乳腺癌的治疗有希望，但死亡率仍然很高，转移性疾病的治疗也很有限。高频不可逆电穿孔（H-FIRE）是一种新型的肿瘤消融技术，其利用高频双极电脉冲来破坏癌细胞膜的稳定性并诱导细胞死亡。然而，目前缺乏有关免疫系统激活以下H-火和其他电穿孔为基础的肿瘤ablationtechnology.Methods的数据：在这里，我们利用小鼠4 T1乳腺肿瘤模型来评估H-火治疗参数对癌症的进展和免疫系统激活在体外和体内。我们进一步表明，局部治疗H-FIRE显着减少4 T1转移。H-FIRE通过与坏死和焦亡相关的非热机制杀死4 T1细胞，导致体外和体内与分子模式信号传导相关的损伤。我们的数据表明，肿瘤消融的水平与细胞免疫的激活增加相关。同样，我们表明，转移性病变的减少是依赖于完整的免疫系统和H-FIRE产生4 T1新抗原，从事适应性免疫系统，以显着减弱tumor progression.Interpretation：细胞死亡和肿瘤消融后H-FIRE治疗激活局部先天免疫系统，这将肿瘤微环境从抗炎状态转变为促炎状态。对癌细胞的非热损伤和增加的先天免疫系统刺激改善了抗原呈递，导致适应性免疫系统的参与和改善的全身抗肿瘤免疫。(C)2019年，任作家。由爱思唯尔公司出版
Background: Despite promising treatments for breast cancer, mortality rates remain high and treatments for metastatic disease are limited. High-frequency irreversible electroporation (H-FIRE) is a novel tumor ablation technique that utilizes high-frequency bipolar electric pulses to destabilize cancer cell membranes and induce cell death. However, there is currently a paucity of data pertaining to immune system activation following H-FIRE and other electroporation based tumor ablation techniques.Methods: Here, we utilized the mouse 4T1 mammary tumor model to evaluate H-FIRE treatment parameters on cancer progression and immune system activation in vitro and in vivo.Findings: H-FIRE effectively ablates the primary tumor and induces a pro-inflammatory shift in the tumor microenvironment. We further show that local treatment with H-FIRE significantly reduces 4T1 metastases. H-FIRE kills 4T1 cells through non-thermal mechanisms associated with necrosis and pyroptosis resulting in damage associated molecular pattern signaling in vitro and in vivo. Our data indicate that the level of tumor ablation correlates with increased activation of cellular immunity. Likewise, we show that the decrease in metastatic lesions is dependent on the intact immune system and H-FIRE generates 4T1 neoantigens that engage the adaptive immune system to significantly attenuate tumor progression.Interpretation: Cell death and tumor ablation following H-FIRE treatment activates the local innate immune system, which shifts the tumor microenvironment from an anti-inflammatory state to a pro-inflammatory state. The non-thermal damage to the cancer cells and increased innate immune system stimulation improves antigen presentation, resulting in the engagement of the adaptive immune system and improved systemic anti-tumor immunity. (C) 2019 The Authors. Published by Elsevier B.V.