NDLI: Comprehensive analysis of the alpha-fetoprotein-specific CD8+ T cell responses in patients with hepatocellular carcinoma.

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Comprehensive analysis of the alpha-fetoprotein-specific CD8+ T cell responses in patients with hepatocellular carcinoma.

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Comprehensive analysis of the alpha-fetoprotein-specific CD8+ T cell responses in patients with hepatocellular carcinoma.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Thimme, Robert Neagu, Michaela Boettler, Tobias Neumann-Haefelin, Christoph Kersting, Nadine Geissler, Michael Makowiec, Frank Obermaier, Robert Hopt, Ulrich T. Blum, Hubert E. Spangenberg, Hans Christian
Description	Country affiliation: Germany Author Affiliation: Thimme R ( Department of Medicine II, University Hospital Freiburg, Freiburg, Germany. robert.thimme@uniklinik-freiburg.de)
Abstract	UNLABELLED: Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide, with a poor prognosis and limited therapeutic options. Therefore, the development of novel therapeutic strategies is of high priority. alpha-Fetoprotein (AFP) is overexpressed in the majority of HCCs. Priming of immune responses against AFP results in significant protective antitumoral T cell responses in the mouse model. Little information is available about the hierarchy, breadth, frequency, and peripheral versus intrahepatic distribution of AFP-specific CD8(+) T cell responses in patients with HCC. To address these important issues we comprehensively analyzed CD8(+) T cell responses against full-length AFP in peripheral blood, tumor liver tissue, and nontumor liver tissue from patients with HCC using overlapping AFP peptides. The AFP-specific CD8(+) T cell response was also tested in peripheral blood and liver from patients chronically infected with hepatitis C virus (HCV) and compared to the HCV-specific CD8(+) T cell response. The majority of patients with HCC showed AFP-specific responses, with many responses directed against previously unreported epitopes. These responses were primarily detectable in the HCC tissue and mainly targeted the C-terminus of AFP. Interestingly, AFP-specific T cells were not only found in patients with HCC but also in patients with chronic HCV infection, other liver diseases, and less frequently in healthy subjects. CONCLUSION: In patients with HCC, a high frequency of AFP-specific CD8(+) T cells directed against different epitopes suggest that AFP has a strong and broad immunogenicity. Further, CD8(+) T cells specific for the self-antigen AFP are present in the normal T cell repertoire and are not centrally or peripherally deleted. Our results provide support for strategies to boost AFP-specific CD8(+) T cell responses in patients with HCC but also demonstrate a diversity of immune responses that may be needed for protection.
File Format	HTM / HTML
ISSN	02709139
Issue Number	6
Volume Number	48
e-ISSN	15273350
Journal	Hepatology
Language	English
Publisher	Wiley
Publisher Date	2008-12-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Discipline Hepatology Cd8-positive T-lymphocytes Metabolism Carcinoma, Hepatocellular Liver Neoplasms Alpha-fetoproteins Adult Aged Pathology Case-control Studies Epitopes, T-lymphocyte Female Humans Liver Male Middle Aged Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Hepatology

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