title: Dendritic cells fused with different pancreatic carcinoma cells induce different T-cell responses.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pathological Diagnostics ; Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Japan.
authors: Yoshiaki
authors: Y
authors: Andoh
authors: Naohiko
authors: N
authors: Makino
authors: Mitsunori
authors: M
authors: Yamakawa
keywords: cytotoxic T lymphocyte; dendritic cell; interleukin-10; pancreatic cancer; regulatory T cell
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