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
• 负责人: NAKAMURA Seiji
• 金额: $ 7.94万
• 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: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470441/
• 关键词: Immunology; Oral squamous cell carcinoma; Cytotoxic T cell; T cell receptor; Cytokine; Tumor-associated antigen; Gene cloning; Vaccination therapy; 細胞障害性T細胞

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 in this research were as follows.1)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.2)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 of TCR Vβ genes used by the T cells recognizing SART-1 is further being performed, and these results will be useful for the establishment of vaccination therapy with SART-1 and also the estimation of its efficacies.

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。主要研究结果如下：1）抗肿瘤T细胞TCR的鉴定：PCR分析显示，限制性Vβ基因家族在肿瘤浸润性淋巴细胞中广泛存在。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。2）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：通过用SART-1肽培养外周血单个核细胞成功地体外诱导识别SART-1的T细胞。用同样的方法分析了T细胞所用的TCR Vβ基因，发现了相似的T细胞克隆型，并进一步对识别SART-1的T细胞所用的TCR Vβ基因进行了DNA测序，这些结果将有助于SART-1疫苗治疗的建立和疗效的评估。

项目成果

Kawamura, E., Nakamura, S., Sasaki, M., Ohyama, Y., Kadena, T., Kumamaru, W., Shirasuna, K.: "Accumulation of oligoclonal T cells in the infiltrating lymphocytes in oral lichen planus"Journal of Oral Pathology & Medicine. 32. 282-289 (2003)

Kawamura, E.、Nakamura, S.、Sasaki, M.、Ohyama, Y.、Kadena, T.、Kumamaru, W.、Shirasuna, K.：“口腔扁平苔藓浸润淋巴细胞中寡克隆 T 细胞的积累”

Kumamaru, W., Nakamura, S., Kadena, T., Yamada, A., Kawamura, E., Sasaki, M., Ohyama, Y., Toyoshima, T., Hayashida, J., Itoh, K., shirasuna, K.: "T cell receptor Vβ gene usage by T cells reactive with the tumor-rejection antigen SART-1 in oral squamous ce

Kumamaru, W.、Nakamura, S.、Kadena, T.、Yamada, A.、Kawamura, E.、Sasaki, M.、Ohyama, Y.、Toyoshima, T.、Hayashida, J.、Itoh, K.、 shirasuna, K.：“口腔鳞状细胞癌中与肿瘤排斥抗原 SART-1 反应的 T 细胞使用 T 细胞受体 Vβ 基因

Kawamura, E., Nakamura, S., et al.: "Accumulation of oligoclonal T cells in the infiltrating lymphocytes in oral lichen planus"Journal of Oral pathology & Medicine. 32. 282-289 (2003)

Kawamura, E.、Nakamura, S.等人：“口腔扁平苔藓浸润淋巴细胞中寡克隆 T 细胞的积累”口腔病理学杂志

Kumamaru, W., Nakamura, S., et al.: "T cell receptor Vβ gene usage by T cells reactive with the tumor-rejection antigen SART-1 in oral squamous cell carcinoma"International Journal of Cancer. 108. 686-695 (2004)

Kumamaru, W., Nakamura, S. 等人：“口腔鳞状细胞癌中与肿瘤排斥抗原 SART-1 反应的 T 细胞对 T 细胞受体 Vβ 基因的使用”，《国际癌症杂志》108。686-695。 (2004)