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不可逆电穿孔联合细胞因子诱导的杀伤细胞治疗荷 Panc02 胰腺癌异种移植瘤小鼠

Combination therapy of irreversible electroporation and cytokine-induced killer cells for treating mice bearing panc02 pancreatic-cancer xenografts.

作者信息

Wang Baohua, Wang Huiyang, Yue Lan, Chen Qiang, Dong Junjie, Jiang Tian'an

机构信息

Department of Ultrasound Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.

Zhejiang CuraWay Medical Technology Co., Ltd., Hangzhou, 310018, China.

出版信息

Biochem Biophys Rep. 2023 Sep 19;35:101547. doi: 10.1016/j.bbrep.2023.101547. eCollection 2023 Sep.

DOI:10.1016/j.bbrep.2023.101547
PMID:37745985
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10514433/
Abstract

The current study aimed to investigate the antitumor effects and potent mechanism of cytokine-induced killer (CIK) cells combined with irreversible electroporation (IRE) via Panc02 cell-bearing mouse model in vivo. CIK cells were isolated from the spleens of Panc02 pancreatic-cancer (PC) subcutaneous-xenograft model and the proportion of different lymphocytes was also determined. The antitumor effect of the combination of IRE and CIK cells in a PC subcutaneous-xenograft model was also investigated. The proportion of cells that were positive for CD3CD8 and the proportion of CD3CD56 cells were both significantly increased after 21 days of culture. Combined treatment of IRE and CIK cell significantly inhibited tumor growth and increased the survival rate of Panc02 cell-bearing mice. Furthermore, infiltration of lymphocytes into tumor tissue was significantly increased by this combination therapy compared with the untreated group or monotherapy group. In addition, IRE significantly enhanced the expression of chemokine receptors elicited by CIK cells. In conclusion, IRE combined with CIK cells showed superior antitumor efficacy in a PC xenograft model, which we attributed to the promotion of lymphocytic infiltration, as well as to upregulation of chemokine receptor expression and the regulators of CIK cell proliferation.

摘要

本研究旨在通过荷Panc02细胞的小鼠体内模型,探讨细胞因子诱导的杀伤(CIK)细胞联合不可逆电穿孔(IRE)的抗肿瘤作用及其潜在机制。从Panc02胰腺癌(PC)皮下异种移植模型的脾脏中分离CIK细胞,并测定不同淋巴细胞的比例。还研究了IRE与CIK细胞联合应用于PC皮下异种移植模型的抗肿瘤效果。培养21天后,CD3CD8阳性细胞比例和CD3CD56细胞比例均显著增加。IRE与CIK细胞联合治疗显著抑制肿瘤生长,提高荷Panc02细胞小鼠的生存率。此外,与未治疗组或单一治疗组相比,这种联合治疗显著增加了淋巴细胞向肿瘤组织的浸润。此外,IRE显著增强了CIK细胞诱导的趋化因子受体的表达。总之,IRE联合CIK细胞在PC异种移植模型中显示出卓越的抗肿瘤疗效,我们将其归因于淋巴细胞浸润的促进,以及趋化因子受体表达的上调和CIK细胞增殖调节剂的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bde/10514433/5f0cb5d8be76/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bde/10514433/d02f367e5f3f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bde/10514433/e08d3697dd7a/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bde/10514433/c2374f6a74f5/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bde/10514433/74adfcb26d79/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bde/10514433/5f0cb5d8be76/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bde/10514433/d02f367e5f3f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bde/10514433/e08d3697dd7a/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bde/10514433/c2374f6a74f5/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bde/10514433/74adfcb26d79/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bde/10514433/5f0cb5d8be76/gr5.jpg

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本文引用的文献

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PD-1 and LAG-3 expression in EBV-associated pediatric Hodgkin lymphoma has influence on survival.程序性死亡受体1(PD-1)和淋巴细胞活化基因3(LAG-3)在与 Epstein-Barr 病毒(EBV)相关的儿童霍奇金淋巴瘤中的表达对生存有影响。
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Imaging and Clinicopathological Features of Acinar Cell Carcinoma.
腺泡细胞癌的影像学与临床病理特征
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The Synergistic Role of Irreversible Electroporation and Chemotherapy for Locally Advanced Pancreatic Cancer.不可逆电穿孔与化疗在局部晚期胰腺癌治疗中的协同作用
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Engagement of the costimulatory molecule ICOS in tissues promotes establishment of CD8 tissue-resident memory T cells.共刺激分子 ICOS 在组织中的结合促进了 CD8 组织驻留记忆 T 细胞的建立。
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