Analysis of pathogenesis and establishment of novel diagnostic strategy of oral mucosal diseases by T cell receptor-based analysis
基于T细胞受体分析的口腔粘膜疾病发病机制分析及新诊断策略的建立
基本信息
- 批准号:15390618
- 负责人:
- 金额:$ 9.28万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:2003
- 资助国家:日本
- 起止时间:2003 至 2006
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
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
本研究旨在鉴定口腔鳞状细胞癌(SCC)中抗肿瘤T细胞上表达的T细胞受体(TCR)及其靶抗原,特别是参与抗肿瘤T细胞活化和/或失活的肿瘤相关抗原。1)口腔鳞状细胞癌免疫调节分子的表达:免疫组化法检测口腔鳞状细胞癌细胞上各种免疫调节分子的表达。结果,在对肿瘤相关抗原肽具有CTL活性的患者中,观察到口腔SCC细胞上CD 80和ICAM-1的异常表达。相反,在没有用任何肽诱导CTL活性的患者中观察到口腔SCC细胞上肿瘤相关抗原RCAS 1的异常表达。在表达RCAS 1的口腔鳞癌细胞周围经常观察到凋亡T细胞,这表明RCAS 1在肿瘤逃避宿主免疫系统的机制中起重要作用。 ...更多信息 疾病特异性TCR基因及其靶抗原的鉴定:基于PCR的分析显示,限制性Vβ基因家族经常用于口腔SCC患者的肿瘤浸润淋巴细胞中。进一步基于SSCP的分析发现在某些Vβ基因家族中T细胞克隆型的寡克隆扩增。正在进行独特TCR基因的DNA测序和表达独特TCR的T细胞克隆的建立。用12种肿瘤相关抗原肽体外培养口腔鳞癌患者外周血单个核细胞,检测其特异性细胞毒性T淋巴细胞(CTL)活性。结果,SART-1最常诱导肽特异性CTL活性<690>。相反,在40%的受检患者中,任何肽均未诱导CTL活性。本研究表明,肿瘤相关抗原肽SART-1<690>在口腔SCC患者的诊断和随访中是最有用的,并且还可用于通过肽疫苗建立癌症免疫治疗。但同时也表明,肿瘤细胞的抗原性和肿瘤逃避宿主免疫系统的机制必须引起重视。少
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Expression of tumor-associated antigen RCAS1 and its possible involvement in immune evasion in oral squamous cell carcinoma.
肿瘤相关抗原RCAS1的表达及其可能参与口腔鳞状细胞癌的免疫逃避。
- DOI:
- 发表时间:2006
- 期刊:
- 影响因子:0
- 作者:Toyoshima;T.;et al.
- 通讯作者:et al.
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NAKAMURA Seiji其他文献
Water Sources of Lake Bottom Springs in Lake Kawaguchi, Northern Foot of Mount Fuji, Japan
日本富士山北麓河口湖湖底泉水源
- DOI:
10.5026/jgeography.129.665 - 发表时间:
2020 - 期刊:
- 影响因子:0
- 作者:
YAMAMOTO Shinya;NAKAMURA Takashi;SERISAWA Yukihiko;NAKAMURA Seiji;YASUDA Taisuke;UCHIYAMA Takashi - 通讯作者:
UCHIYAMA Takashi
NAKAMURA Seiji的其他文献
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{{ truncateString('NAKAMURA Seiji', 18)}}的其他基金
Generation and migration of plasma-induced defects in III-nitride semiconductors
III族氮化物半导体中等离子体诱导缺陷的产生和迁移
- 批准号:
26390056 - 财政年份:2014
- 资助金额:
$ 9.28万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Saliva as a potential tool for diagnosis of dry mouth including Sjogren's syndrome
唾液作为诊断口干(包括干燥综合征)的潜在工具
- 批准号:
23659949 - 财政年份:2011
- 资助金额:
$ 9.28万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Study on advanced hydrogen sensors based on field effect transistor structure
基于场效应晶体管结构的先进氢传感器研究
- 批准号:
21760052 - 财政年份:2009
- 资助金额:
$ 9.28万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Development of early-diagnosis and made-to-order immunotherapy fororal cancers by using cancer-specific peptides
使用癌症特异性肽开发口腔癌的早期诊断和定制免疫疗法
- 批准号:
20390518 - 财政年份:2008
- 资助金额:
$ 9.28万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Analysis of pathogenesis and establishment of novel diagnostic strategy of oral mucosal diseases by T cell receptorbased analysis
基于T细胞受体分析的口腔粘膜疾病发病机制分析及新诊断策略的建立
- 批准号:
13557179 - 财政年份:2001
- 资助金额:
$ 9.28万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Identification of oral squamous cell carcinoma-associated antigens recognized by T cells
T 细胞识别的口腔鳞状细胞癌相关抗原的鉴定
- 批准号:
12470441 - 财政年份:2000
- 资助金额:
$ 9.28万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Identification of oral squamous cell carcinoma-associated antigens recognized by T cells
T 细胞识别的口腔鳞状细胞癌相关抗原的鉴定
- 批准号:
09470458 - 财政年份:1997
- 资助金额:
$ 9.28万 - 项目类别:
Grant-in-Aid for Scientific Research (B)