Identification of oral squamous cell carcinoma-associated antigens recognized by T cells

以T细胞为主的免疫应答被认为在宿主对肿瘤细胞的防御机制中起着核心作用。本研究旨在鉴定T细胞受体（TCR）和识别T细胞抗原对口腔鳞状细胞癌的作用。目前得到的结果如下：1)抗肿瘤T细胞的特征：在肿瘤浸润淋巴细胞、区域淋巴结和转移淋巴结中，经常检测到活化的T细胞，并以Th1和Th0细胞因子为主。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，肿瘤浸润淋巴细胞中经常使用限制性Vβ基因家族。进一步基于sscp的分析发现，在一些Vβ基因家族中T细胞克隆型存在低克隆扩增。区域淋巴结的分析结果几乎相同。目前正在确定T细胞克隆型的TCR Vβ基因的DNA序列。3)体外诱导识别T细胞-1识别鳞癌抗原的T细胞（SART-1）：通过培养含有SART-1肽的外周血单个核细胞，成功诱导识别SART-1的T细胞。用上述方法分析T细胞使用的TCR Vβ基因，发现包含相似的T细胞克隆型。DNA测序也正在进行，以证明T细胞克隆型包括在肿瘤浸润淋巴细胞和区域淋巴结。虽然没有达到本研究的所有目的，但TCR的鉴定和T细胞对口腔鳞状细胞癌的抗原识别仍有待进一步研究。

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.