Tim-1是主要表达在CD4+T细胞并参与T细胞活化的重要协同刺激分子，我们最新的研究表明，在接种肿瘤疫苗的小鼠中Tim-1表达于肿瘤浸润CD8+T细胞。由于CD8+T细胞是杀伤肿瘤的主要效应细胞，研究Tim-1促进CD8+T细胞抗肿瘤效应的作用机制，对提高肿瘤过继细胞治疗的疗效具有重要意义。 本项目拟在前期工作基础上，结合临床样本深入分析Tim-1+CD8+T细胞在肠癌组织中的分布特征、临床意义及效应功能；体外实验采用抗体干预及染色质免疫共沉淀技术，探讨Tim-1在肠癌浸润CD8+T细胞抗肿瘤效应中的作用及调控机制；体内实验应用Tim-1 基因敲除小鼠及OVA/OT-I模型，验证Tim-1介导CD8+T细胞抗肿瘤免疫应答在肠癌过继细胞治疗中的作用。本研究将进一步阐述Tim-1在CD8+T细胞抗肿瘤免疫应答中的作用机制，为Tim-1作为肠癌过继细胞治疗的靶点提供理论依据与实验基础。

Tim-1 is an important co-stimulatory molecule which contributes to T cell activation, and is mainly expressed on CD4+ T cells. However, our recent data indicated that Tim-1 could also be expressed on tumor infiltrating CD8+ T cells after tumor vaccination. The CD8+ T cell is the major subset of effector cells involved anti-tumor immune response, thus it's important for us to study the contribution and the mechanism of Tim-1 in the enhancement of CD8+ T cell mediated anti-tumor response, which will help improving adoptive T cell therapy of human cancers. Based on our previous data, in this proposal, we aim to further investigate the distribution, the clinical significance and the effector function of Tim-1+CD8+ T cells infiltrating human colorectal cancer tissues. And to study the contribution and the mechanism of Tim-1 in CD8+ T cell-mediated anti-tumor immune response in vitro using various anti-Tim-1 antibodies. We will also study the transcription factors that regulate Tim-1 expression using chromatin immunoprecipitation assay. In addition, the Tim-1 knockout mice and OVA/OT-I model system will be used to determine the contribution of Tim-1 in adoptive cell therapy against colorectal cancer in vivo. Our study will establish the role of Tim-1 in enhancing the effector function of tumor infiltrating CD8+T cell, elucidate the mechanism by which Tim-1 regulates CD8+T cell-mediated anti-tumor immune responses, and provide theoretical and experimental basis for targeting TIM-1 for promoting immunotherapy of cancer.