Analysis of pathogenesis and establishment of novel diagnostic strategy of oral mucosal diseases by T cell receptor-based analysis
| Project/Area Number |
15390618
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Kyushu University |
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Principal Investigator |
NAKAMURA Seiji Kyushu University, Faculty of Dental Science, Professor (60189040)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Hiroki Saga University, Faculty of Medicine, Professor (40260715)
SHIRASUNA Kanemitsu KYUSHU UNIVERSITY, Faculty of Dental Science, Professor (30093420)
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| Project Period (FY) |
2003 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2006: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2003: ¥5,500,000 (Direct Cost: ¥5,500,000)
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| Keywords | Immunity / Oral squamous cell carcinome / T cell / Tumor-associated antigen / Cytokine / Activation / Inactivation / Sjogren's syndrome |
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| Research Abstract |
This research was addressed to identify T cell receptors (TCR) expressed on anti-tumor T cells and their target antigens, especially tumor-associated antigens involved in activation and/or inactivation of anti-tumor T cells in oral squamous cell carcinoma (SCC). Results obtained in this research were as follows:
1) Expression of immune-regulating molecules by oral SCC: Expression of various immune-regulating molecules on oral SCC cells was immunohistochemically examined. As a result, in patients in whom CTL activities against tumor-associated antigenic peptides, an aberrant expression of CD80 and ICAM-1 on oral SCC cells was observed. In contrast, an aberrant expression of tumor-associated antigen RCAS1 on oral SCC cells was observed in patients in whom no CTL activity was induced with any peptides. Apoptotic T cells were frequently observed around oral SCC cells expressing RCAS1, suggesting RCAS1 plays an important role in the tumor escape mechanism from the host immune system.
2) Ident
… More
ification of disease-specific TCR genes and their target antigens: PCR-based analysis revealed that restricted Vβ gene families are frequently used in tumor-infiltrating lymphocytes of patients with oral SCC. Further SSCP-based analysis found oligoclonal expansion of T cell clonotypes in some Vβ gene families. DNA sequencing of the unique TCR genes and establishment of T cell clones expressing the unique TCR are being performed. Peripheral blood mononuclear cells from patients with oral SCC were cultured in vitro with 12 kinds of tumor-associated antigenic peptides, and were then examine their peptide-specific cytotoxic T lymphocyte (CTL) activities. As a result, peptide-specific CTL activities were most frequently induced with SART-l_<690>. In contrast, in40% of the patients examined, no CTL activity was induced with any peptides.
This research indicated that tumor-associated antigenic peptide SART-l_<690> is most useful in the diagnosis and follow-up of patients with oral SCC, and also for the establishment of cancer immunotherapy by peptide vaccination. However, it was also indicated that the antigenicity of tumor cells and the tumor escape mechanism from the host immune system must be paid attention. Less
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Report
(5 results)
Research Products
(4 results)
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[Journal Article] Expression of tumor-associated antigen RCAS1 and its possible involvement in immune evasion in oral squamous cell carcinoma.2006
Author(s)
Toyoshima, K., Nakamura, S., Kumamaru, W., Kawamura, E., Ishibashi, H., Hayashida, J.-N., Moriyama, M., Ohyama, Y., Sasaki, M., Shirasuna, K.
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Journal Title
Journal of Oral Pathology & Medicine 35
Pages: 361-368
Description
「研究成果報告書概要(欧文)」より
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