Wang Baohua, Wang Huiyang, Yue Lan, Chen Qiang, Dong Junjie, Jiang Tian'an
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.
Biochem Biophys Rep. 2023 Sep 19;35:101547. doi: 10.1016/j.bbrep.2023.101547. eCollection 2023 Sep.
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.
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。