Department of Pathological Diagnostics ; Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Japan.
Onco Targets Ther. 2013;6:29-40. doi: 10.2147/OTT.S37916. Epub 2013 Jan 22.
It is unclear whether there are any differences in the induction of cytotoxic T lymphocytes (CTL) and CD4(+)CD25(high) regulatory T-cells (Tregs) among dendritic cells (DCs) fused with different pancreatic carcinomas. The aim of this study was to compare the ability to induce cytotoxicity by human DCs fused with different human pancreatic carcinoma cell lines and to elucidate the causes of variable cytotoxicity among cell lines.
Monocyte-derived DCs, which were generated from peripheral blood mononuclear cells (PBMCs), were fused with carcinoma cells such as Panc-1, KP-1NL, QGP-1, and KP-3L. The induction of CTL and Tregs, and cytokine profile of PBMCs stimulated by fused DCs were evaluated.
The cytotoxicity against tumor targets induced by PBMCs cocultured with DCs fused with QGP-1 (DC/QGP-1) was very low, even though PBMCs cocultured with DCs fused with other cell lines induced significant cytotoxicity against the respective tumor target. The factors causing this low cytotoxicity were subsequently investigated. DC/QGP-1 induced a significant expansion of Tregs in cocultured PBMCs compared with DC/KP-3L. The level of interleukin-10 secreted in the supernatants of PBMCs cocultured with DC/QGP-1 was increased significantly compared with that in DC/KP-3L. Downregulation of major histocompatibility complex class I expression and increased secretion of vascular endothelial growth factor were observed with QGP-1, as well as in the other cell lines.
The present study demonstrated that the cytotoxicity induced by DCs fused with pancreatic cancer cell lines was different between each cell line, and that the reduced cytotoxicity of DC/QGP-1 might be related to the increased secretion of interleukin-10 and the extensive induction of Tregs.
目前尚不清楚融合不同胰腺癌细胞系的树突状细胞（DC）在诱导细胞毒性 T 淋巴细胞（CTL）和 CD4+CD25+调节性 T 细胞（Treg）方面是否存在差异。本研究旨在比较融合不同人胰腺癌细胞系的人 DC 诱导细胞毒性的能力，并阐明细胞系间细胞毒性差异的原因。
从外周血单核细胞（PBMC）中生成单核细胞来源的 DC，然后与 Panc-1、KP-1NL、QGP-1 和 KP-3L 等癌细胞融合。评估融合 DC 刺激的 PBMC 诱导 CTL 和 Treg 的能力以及细胞因子谱。
与融合了其他细胞系的 DC 共培养的 PBMC 相比，与融合了 QGP-1 的 DC（DC/QGP-1）共培养的 PBMC 对肿瘤靶标诱导的细胞毒性非常低。随后研究了导致这种低细胞毒性的因素。与融合了 KP-3L 的 DC 相比，DC/QGP-1 诱导共培养的 PBMC 中 Treg 的显著扩增。与融合了 KP-3L 的 DC 相比，与 DC/QGP-1 共培养的 PBMC 上清液中白细胞介素-10 的分泌水平显著增加。QGP-1 及其他细胞系均观察到主要组织相容性复合体 I 表达下调和血管内皮生长因子分泌增加。
本研究表明，融合胰腺癌细胞系的 DC 诱导的细胞毒性在各细胞系之间存在差异，而 DC/QGP-1 降低的细胞毒性可能与白细胞介素-10 的分泌增加和 Treg 的广泛诱导有关。
