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
• 负责人: NAKAMURA Seiji
• 金额: $ 5.76万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470458/
• 关键词: Immunity; Oral squamous cell carcinoma; Cytotoxic T cells; T cell receptor; Cytokine; Tumor-associated antigen; Gene cloning; T細胞クローン

Immune response mainly by T cells is considered to play a central role in the host defense mechanisms against tumor cells. This study was addressed to identify T cell receptor (TCR) and recognizing antigen of T cells against oral squamous cell carcinoma. Results obtained so far are as follows.1) Characterization of anti-tumor T cells : In tutmor-infiltrating lymphocytes, regional lymph nodes, and metastatic lymph nodes, activated T cells were frequently detected and Th1 and Th0 cytokines were dominantly produced. Especially production of IFN-γ was closely associated with the presence of activated T cells.2) Identification of TCR of anti-tumor T cells : PCR-based analysis revealed that restricted Vβ gene families are frequently used in tumor-infiltrating lymphocytes. Further SSCP-based analysis found oligoclonal expansion of T cell clonotypes in some Vβ gene families. Almost same results were obtained by analyses in regional lymph nodes. DNA sequence of TCR Vβ genes of the T cell clonotypes is now being determined.3) In vitro induction of T cells recognizing squamous cell carcinoma antigen recognized by T cells-1 (SART-1) : In vitro induction of T cells recognizing SART-1 was successful by culture of peripheral blood mononuclear cells with SART-1 peptides. TCR Vβ genes used by the T cells were analyzed by same methods as mentioned above and similar T cell clonotypes were found to be included. DNA sequencing is also being performed to demonstrate that the T cell clonotypes are included in tumorinfiltrating lymphocytes and regional lymph nodes.Although all of the purposes in this study were not achieved, identification of TCR and recognizing antigen of T cells against oral squamous cell carcinoma is to be continued.

主要通过T细胞的免疫应答被认为在宿主对肿瘤细胞的防御机制中起核心作用。本研究旨在鉴定抗口腔鳞癌T细胞受体（TCR）及其识别抗原。目前获得的结果如下：1）抗肿瘤T细胞的特性：在肿瘤浸润淋巴细胞、局部淋巴结和转移淋巴结中，经常检测到活化的T细胞，并且主要产生Th 1和Th 0细胞因子。特别是IFN-γ的产生与活化T细胞的存在密切相关。2）抗肿瘤T细胞TCR的鉴定：基于PCR的分析显示，限制性Vβ基因家族经常用于肿瘤浸润淋巴细胞。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。区域淋巴结分析结果基本一致。T细胞克隆型TCR Vβ基因的DNA序列正在测定中。3）识别T细胞识别的鳞状细胞癌抗原-1（SART-1）的T细胞的体外诱导：用SART-1肽段培养外周血单个核细胞，成功诱导识别SART-1的T细胞。通过与上述相同的方法分析T细胞使用的TCR Vβ基因，发现包括相似的T细胞克隆型。虽然本研究的目的尚未全部达到，但口腔鳞癌TCR的鉴定和T细胞识别抗原的鉴定仍需继续。