In vitro generation of cytotoxic and regulatory T cells by fusions of human dendritic cells and hepatocellular carcinoma

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In vitro generation of cytotoxic and regulatory T cells by fusions of human dendritic cells and hepatocellular carcinoma cells Shigeo Koido*1,2, Sadamu Homma3, Eiichi Hara5, Makoto Mitsunaga1, Yoshihisa Namiki2, Akitaka Takahara1,3, Eijiro Nagasaki3, Hideo Komita1, Yukiko Sagawa4, Toshifumi Ohkusa1,2, Kiyotaka Fujise1,2, Jianlin Gong6 and Hisao Tajiri1 Address: 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan, 2Institute of Clinical Medicine and Research, The Jikei University School of Medicine, Tokyo, Japan, 3Department of Oncology, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan, 4Clinical Data Bank, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan, 5Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama, Japan and 6Department of Medicine, Boston University School of Medicine, Boston, MA, USA Email: Shigeo Koido* - [email protected]; Sadamu Homma - [email protected]; Eiichi Hara - [email protected]; Makoto Mitsunaga - [email protected]; Yoshihisa Namiki - [email protected]; Akitaka Takahara - [email protected]; Eijiro Nagasaki - [email protected]; Hideo Komita - [email protected]; Yukiko Sagawa - [email protected]; Toshifumi Ohkusa - [email protected]; Kiyotaka Fujise - [email protected]; Jianlin Gong - [email protected]; Hisao Tajiri - [email protected] * Corresponding author

Published: 15 September 2008 Journal of Translational Medicine 2008, 6:51

doi:10.1186/1479-5876-6-51

Received: 29 June 2008 Accepted: 15 September 2008

This article is available from: http://www.translational-medicine.com/content/6/1/51 © 2008 Koido et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract Background: Human hepatocellular carcinoma (HCC) cells express WT1 and/or carcinoembryonic antigen (CEA) as potential targets for the induction of antitumor immunity. In this study, generation of cytotoxic T lymphocytes (CTL) and regulatory T cells (Treg) by fusions of dendritic cells (DCs) and HCC cells was examined. Methods: HCC cells were fused to DCs either from healthy donors or the HCC patient and investigated whether supernatants derived from the HCC cell culture (HCCsp) influenced on the function of DCs/HCC fusion cells (FCs) and generation of CTL and Treg. Results: FCs coexpressed the HCC cells-derived WT1 and CEA antigens and DCs-derived MHC class II and costimulatory molecules. In addition, FCs were effective in activating CD4+ and CD8+ T cells able to produce IFN-γ and inducing cytolysis of autologous tumor or semiallogeneic targets by a MHC class I-restricted mechanism. However, HCCsp induced functional impairment of DCs a