Analysis of pathogenesis and establishment of novel diagnostic strategy of oral mucosal diseases by T cell receptorbased analysis
| Project/Area Number |
13557179
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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 | 展開研究 |
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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 Dentistry, Assistant Professor, 大学病院, 講師 (60189040)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRASUNA Kanemitsu KYUSHU UNIVERSITY, Faculty of Dentistry, Professor, 歯学研究院, 教授 (30093420)
岸原 健二 九州大学, 生体防御医学研究所, 助手 (80214774)
嘉手納 勉 九州大学, 歯学部・附属病院, 助手 (30325469)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2003: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2002: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2001: ¥5,800,000 (Direct Cost: ¥5,800,000)
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| Keywords | Immunology / Oral mucosal disease / T cell receptor / Antigen / Cytokine / Diagnosis / Oral lichen planus / Sjogren's syndrome / シェーグレン症侯群 / 口腔扁平上皮癌 / 遺伝子クローニング / T細胞 / 臨床検査 |
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| Research Abstract |
This research was addressed to identify a disease-specific T cell receptor (TCR) in oral mucosal diseases and to establish a diagnostic strategy by examining the presence of disease-specific T cells expressing the TCR in patients with the diseases. Results obtained in this research were as follows :
1)Identification of disease-specific TCR genes : PCR-based analysis revealed that restricted Vβ gene families are frequently used in tumor-infiltrating lymphocytes of patients with oral squamous cell carcinoma (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.
2)Induction of T cells recognizing tumor-associated antigenic peptides from peripheral blood of patients with oral SCC : Peripheral blood mononuclear cells from patients with oral SCC were cultured in vitro with 13 kinds of tumor-associated antigenic peptides,
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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-1_<690>, SARI-2_<93>, and ART4_<75>. CTL activities against other peptides also tended to be inducible from patients in whom CTL activities against SART-1_<690>, SARI-2_<93>, and ART4_<75> were induced. In contrast, in 40% of the patients examined, no CTL activity was induced with any peptides.
3)Expression of immune-regulating molecules in the lesions of patients with oral SCC : Expression of, various immune-regulating molecules in the lesions 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 SCC cells was observed. In contrast, an aberrant expression of tumor-associated antigen RCASI on SCC cells was observed in patients in whom no CTL activity was induced with any peptides. Apoptotic T cells were frequently observed around SCC cells expressing RCAS1, suggesting RCASI plays an important role in the tumor escape mechanism from the host immune system.
This research indicated that tumor-associated antigenic peptides including SARI-1_<690>, SART-2_<93>, and ART4_<75> are 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 antigenecity of tumor cells and the tumor escape mechanism from the host immune system must be paid attention. Novel diagnostic strategy to quantify the presence of disease-specific T cells in the lesions or peripheral blood from patients with various oral mucosal diseases is being also established. Less
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Report
(4 results)
Research Products
(6 results)
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[Journal Article] T cell receptor Vβ gene usage by T cells reactive with the tumor-rejection antigen SARI-1 in oral squamous cell carcinoma.2004
Author(s)
Kumamaru, W., Nakamura, S., Kadena, T., Yamada, A., Kawamura, E., Sasaki, M., Ohyama, Y., Toyoshima, T., Hayashida, J., Itoh, K., Shirasuna, K.
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Journal Title
International Journal of Cancer 108
Pages: 686-695
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Accumulation of oligoclonal T cells in the infiltrating lymphocytes in oral lichen planus.2003
Author(s)
Kawamura, E., Nakamura, S., Sasaki, M., Ohyama, Y., Kadena, T., Kumamaru, W., Shirasuna, K.
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Journal Title
Journal of Oral Pathology & Medicine 32
Pages: 282-289
Description
「研究成果報告書概要(欧文)」より
Related Report
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