不可逆电穿孔联合免疫疗法治疗实体瘤的研究进展  

Progress on irreversible electroporation combined with immunotherapy in the treatment of solid tumors

作　　者：张娜娜 张炜[4] 毛璐婧 韩轩 吕毅[1,2,3,4] Nana Zhang;Wei Zhang;Lujing Mao;Xuan Han;Yi Lü(Institute of Regenerative and Reconstructive Medicine,Med-X Institute,First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710049,China;National Local Joint Engineering Research Center for Precision Surgery&Regenerative Medicine,First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China;Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering,First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China;Department of Hepatobiliary Surgery,First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China)

机构地区：[1]西安交通大学第一附属医院Med-X研究院再生与重建医学研究所,西安710049 [2]西安交通大学第一附属医院精准外科与再生医学国家地方联合工程研究中心,西安710061 [3]西安交通大学第一附属医院陕西省再生医学与外科工程研究中心,西安710061 [4]西安交通大学第一附属医院肝胆外科,西安710061

出　　处：《科学通报》2021年第34期4368-4377,共10页Chinese Science Bulletin

基　　金：国家重点研发计划(2018YFC0115300);国家重大科学仪器研制项目(81727802)资助。

摘　　要：不可逆电穿孔(irreversible electroporation, IRE)是近年来新兴的非热消融技术,因其不引起热损伤,避免了"热沉效应",在实体瘤的治疗上具有很好的应用前景.但IRE因消融效果不彻底、易出现复发等因素限制了其临床应用.然而IRE通过高频短脉冲在细胞膜上形成不可逆的纳米级穿孔,不仅可直接杀伤肿瘤细胞,且细胞内隐蔽肿瘤抗原的大量释放可促使肿瘤细胞变成原位"肿瘤疫苗",诱发潜在的抗肿瘤免疫反应,有助于杀伤消融后残余的肿瘤细胞并抑制肿瘤的局部复发与转移,为IRE联合免疫疗法治疗恶性肿瘤奠定了基础.本文主要围绕IRE诱导荷瘤机体的肿瘤局部和全身性免疫反应的特点及其相关机制,以及IRE联合免疫疗法治疗实体瘤效果的研究进展进行综述,以期为IRE联合免疫疗法治疗实体瘤的临床应用提供理论与实践指导.The advent of medical engineering technologies such as electromagnetism, acoustics or optics tumor ablation technology coupled with their clinical applications has gained a lot of interest among scientists. Irreversible electroporation(IRE), a novel physical ablation technique, is widely utilized to ablate the unresectable solid tumors and demonstrates a favorable safety and high efficacy in clinical applications, which is a promising therapy in clinical cancer treatment. As opposed to thermal ablative techniques, IRE induces cell death by the delivery of high-voltage electrical pulses, which possesses several advantages as a non-thermal ablation method:(1) Less collateral thermal damage, especially for the vital nerves/vessels and luminal structure;(2) no heat sink effect, it avoids the energy reduction caused by blood flow that would lead to the incomplete ablation;(3) preservation of extracellular matrix(ECM) scaffold, it is important for promoting rapid postoperative recovery. While a major drawback, the challenge for IRE, is the susceptibility to recurrence resulting from the incomplete ablation, which limits the clinical application of IRE.However, IRE utilizes electric pulses to alter the transmembrane voltage on the cell membrane, which causes nanometersized membrane defects or pores in the cells and leads to loss of cell homeostasis. IRE has been demonstrated to not only kill tumor cells directly, but also promote the massive release of intracellular concealed tumor antigens that become an in situ “tumor vaccine”, inducing a potential anti-tumor immune response to kill residual tumor cells after ablation and inhibiting the local recurrence of tumors. Therefore, IRE can be regarded as a potential immunomodulatory therapy. IRE combined with immunotherapy will be a promising therapeutic strategy for malignant tumors. Recently, researchers paid much more attention to studying the immune response induced by IRE. And several studies have confirmed that IRE can induce a significant immune response in tumor-

关 键 词：不可逆电穿孔 免疫疗法 实体瘤 联合治疗 

分 类 号：R730.5[医药卫生—肿瘤]