The role of reactive oxygen species in the immunity induced by nano-pulse stimulation.

The role of reactive oxygen species in the immunity induced by nano-pulse stimulation.
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DOI:
10.1038/s41598-021-03342-4
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发表时间:
2021-12-09
期刊:
影响因子:
4.6
通讯作者:
Semenov I
Semenov I
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Guo S;Burcus NI;Scott M;Jing Y;Semenov I

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活性氧(ROS)是用纳米脉冲刺激(Nano-Pulse Stimulation,NPSV)治疗的肿瘤细胞的副产物。最近,ROS已被认为是免疫原性细胞死亡和T细胞介导的免疫的一个促成因素。本研究进一步探讨了NPS诱导的活性氧在抗肿瘤免疫中的作用。使用三种检测试剂,即Amplex Red、MitoSox Red和Dihydroethidium,表征4 T1-luc乳腺癌细胞中的ROS产生。在存在或不存在ROS清除剂和/或抗氧化剂的情况下评估ROS淬灭的效率。通过离体树突状细胞活化、体内疫苗接种试验和原位疫苗接种与肿瘤消融来评估经顺铂处理的肿瘤细胞的免疫原性。我们发现,免疫球蛋白治疗增强4 T1-luc小鼠乳腺肿瘤的免疫原性,导致有效的原位疫苗接种保护和诱导长期T细胞免疫。ROS的产生是一个电脉冲剂量依赖性的现象,从ESTA处理的乳腺癌细胞。值得注意的是,过氧化氢产生的动态模式与超氧阴离子产生的动态模式不同。有趣的是,无论用哪种ROS清除剂治疗,不同的ROS清除剂都可以阻断或促进ROS的产生,刺激或抑制肿瘤细胞的生长。阻断活性氧的产生不影响树突状细胞的活化。用经抗氧化剂处理的癌细胞进行体内接种的结果表明,ROS的产生不是免疫保护的先决条件。
Reactive oxygen species (ROS) are byproducts of tumor cells treated with Nano-Pulse Stimulation (NPS). Recently, ROS have been suggested as a contributing factor in immunogenic cell death and T cell-mediated immunity. This research further investigated the role of NPS induced ROS in antitumor immunity. ROS production in 4T1-luc breast cancer cells was characterized using three detection reagents, namely, Amplex Red, MitoSox Red, and Dihydroethidium. The efficiency of ROS quenching was evaluated in the presence or absence of ROS scavengers and/or antioxidants. The immunogenicity of NPS treated tumor cells was assessed by ex vivo dendritic cell activation, in vivo vaccination assay and in situ vaccination with NPS tumor ablation. We found that NPS treatment enhanced the immunogenicity of 4T1-luc mouse mammary tumor, resulted in a potent in situ vaccination protection and induced long-term T cell immunity. ROS production derived from NPS treated breast cancer cells was an electric pulse dose-dependent phenomenon. Noticeably, the dynamic pattern of hydrogen peroxide production was different from that of superoxide production. Interestingly, regardless of NPS treatment, different ROS scavengers could either block or promote ROS production and stimulate or inhibit tumor cell growth. The activation of dendritic cells was not influenced by blocking ROS generation. The results from in vivo vaccination with NPS treated cancer cells suggests that ROS generation was not a prerequisite for immune protection.
DOI: 10.1038/s41598-017-04650-4
发表时间: 2017-07-04
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