| Cytotoxic T cell responses to human telomerase reverse transcriptase in patients with hepatocellular carcinoma. | |
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MedLine Citation:
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PMID: 16729333 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Human telomerase reverse transcriptase, hTERT, has been identified as the catalytic enzyme required for telomere elongation. hTERT is expressed in most tumor cells but seldom expressed in most human adult cells. It has been reported that 80% to 90% of hepatocellular carcinomas (HCCs) express hTERT, making the enzyme a potential target in immunotherapy for HCC. In the current study, we identified hTERT-derived, HLA-A*2402-restricted cytotoxic T cell (CTL) epitopes and analyzed hTERT-specific CTL responses in patients with HCC. Peptides containing the epitopes showed high affinity to bind HLA-A*2402 in a major histocompatibility complex binding assay and were able to induce hTERT-specific CTLs in both hTERT cDNA-immunized HLA-A*2402/Kb transgenic mice and patients with HCC. The CTLs were able to kill hepatoma cell lines depending on hTERT expression levels in an HLA-A*2402-restricted manner and induced irrespective of hepatitis viral infection. The number of single hTERT epitope-specific T cells detected by ELISPOT assay was 10 to 100 specific cells per 3 x 10(5) PBMCs, and positive T cell responses were observed in 6.9% to 12.5% of HCC patients. hTERT-specific T cell responses were observed even in the patients with early stages of HCC. The frequency of hTERT/tetramer+ CD8+ T cells in the tumor tissue of patients with HCC was quite high, and they were functional. In conclusion, these results suggest that hTERT is an attractive target for T-cell-based immunotherapy for HCC, and the identified hTERT epitopes may be valuable both for immunotherapy and for analyzing host immune responses to HCC. |
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Authors:
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Eishiro Mizukoshi; Yasunari Nakamoto; Yohei Marukawa; Kuniaki Arai; Tatsuya Yamashita; Hirokazu Tsuji; Kiyotaka Kuzushima; Masafumi Takiguchi; Shuichi Kaneko |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Hepatology (Baltimore, Md.) Volume: 43 ISSN: 0270-9139 ISO Abbreviation: Hepatology Publication Date: 2006 Jun |
Date Detail:
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Created Date: 2006-05-31 Completed Date: 2006-07-13 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8302946 Medline TA: Hepatology Country: United States |
Other Details:
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Languages: eng Pagination: 1284-94 Citation Subset: IM |
Affiliation:
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Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carcinoma, Hepatocellular / genetics, immunology*, pathology, therapy Cell Line, Tumor Cytotoxicity, Immunologic DNA, Complementary / analysis DNA-Binding Proteins / immunology, pharmacology* Disease Models, Animal Epitopes Female Flow Cytometry HLA Antigens / immunology Humans Immunotherapy / methods Liver Neoplasms / genetics, immunology*, pathology, therapy Male Mice Mice, Transgenic Probability Protein Binding Reference Values Sensitivity and Specificity T-Lymphocytes, Cytotoxic / immunology* Telomerase / immunology, pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/DNA, Complementary; 0/DNA-Binding Proteins; 0/Epitopes; 0/HLA Antigens; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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