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Cytokine-induced killer cells co-cultured with dendritic cells loaded with the protein lysate produced by radiofrequency ablation induce a specific antitumor response

机译:细胞因子诱导的杀伤细胞与负载有射频消融产生的蛋白质裂解物的树突状细胞共培养诱导特异性抗肿瘤反应

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摘要

Radiofrequency ablation (RFA) causes coagulative necrosis of tumor tissue and the production of local tumor protein debris. These fragments of tumor protein debris contain a large number of various antigens, which can stimulate a specific cellular immune response. In the present study, dendritic cells (DCs) were loaded with tumor protein lysate antigens that were produced in situ by RFA, and were used to treat murine colon carcinoma in combination with cytokine-induced killer (CIK) cells. Subsequent to the treatment of murine colon carcinoma by RFA, the in situ supernatant of tumor lysis was collected and the DCs were loaded with the lysate antigen to generate Ag-DCs. CIK cells induced from the spleen cells of mice were co-cultured with Ag-DCs to generate Ag-DC-CIK cells. The results revealed that the Ag-DC-CIK cells exhibited strong antitumor activity in vitro and in vivo. The morphology and immunophenotypes of these cells were determined using microscopy and flow cytometry, respectively. The cytotoxic activity of Ag-DC-CIK cells was determined using a CCK-8 assay. To establish a mouse model, mice were randomized into Ag-DC-CIK, DC-CIK, CIK and PBS control groups and monitored for tumor growth and survival time. ANOVA was used to compare the trends in the three groups for implanted tumor volumes. The log-rank test was used to compare the survival time. The present findings indicated that DCs loaded with the protein lysate antigens of tumors, produced in situ by RFA, combined with CIK cells may be a novel strategy for cancer treatment.
机译:射频消融(RFA)会引起肿瘤组织的凝固性坏死和局部肿瘤蛋白碎片的产生。肿瘤蛋白碎片的这些片段包含大量的各种抗原,这些抗原可以刺激特定的细胞免疫反应。在本研究中,树突状细胞(DCs)装有由RFA原位产生的肿瘤蛋白裂解物抗原,并与细胞因子诱导的杀伤(CIK)细胞联合用于治疗鼠类结肠癌。在通过RFA治疗鼠类结肠癌之后,收集肿瘤裂解的原位上清液,并将裂解物抗原上样至DC,产生Ag-DC。将由小鼠脾细胞诱导的CIK细胞与Ag-DC共培养以产生Ag-DC-CIK细胞。结果表明,Ag-DC-CIK细胞在体外和体内均表现出强的抗肿瘤活性。这些细胞的形态和免疫表型分别使用显微镜和流式细胞仪确定。使用CCK-8测定法测定Ag-DC-CIK细胞的细胞毒性活性。为了建立小鼠模型,将小鼠随机分为Ag-DC-CIK,DC-CIK,CIK和PBS对照组,并监测肿瘤的生长和存活时间。方差分析用于比较三组植入肿瘤体积的趋势。对数秩检验用于比较生存时间。目前的发现表明,由RFA原位产生的,载有肿瘤蛋白裂解物抗原的DC与CIK细胞结合可能是一种新的癌症治疗策略。

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