免疫细胞表面分子TIM-3/CEACAM1共表达对结直肠癌的诊断及预后研究

免疫检查点TIM-3上调和肿瘤的免疫逃避密切相关，CEACAM1作为TIM-3的异嗜性配体，可以调控TIM-3介导的T细胞耗竭，致肿瘤免疫耐受。申请者前期研究发现：TIM-3和CEACAM1在结直肠癌患者的循环CD8+T细胞及肿瘤组织的肿瘤浸润淋巴细胞上存在共表达，介导了结直肠癌病人的T细胞功能耗竭，同时TIM-3/CEACAM1共表达的T细胞比例在结直肠癌远处转移患者中明显高于无远处转移患者。因此，本项目通过检测结直肠癌病人外周血、原发灶及转移灶临床标本，分析TIM-3及CEACAM1在未/已转移结直肠癌T细胞中表达的差异，并建立TIM-3/CEACAM1对结直肠癌的预测模型。通过结直肠癌细胞系与T细胞共培养体系、小鼠结直肠癌转移模型等体内外模型，探讨TIM-3/CEACAM1对肿瘤生长，转移及预后的影响，为结直肠癌转移的免疫治疗提供潜在的新靶点。

Upregulation of TIM-3 is associated with immune escape. It has been reported that CEACAM1 can regulate T cell exhaustion via TIM-3 molecule, which will lead to the immune tolerance of tumors. Our previous work indicated that TIM-3 and CEACAM1 were co-expressed on the circulating CD8+ T cells and tumor-infiltrating lymphocytes, which would cause T cell exhaustion of colorectal cancer (CRC) patients, and we showed that the number of T cells which co-expressed TIM-3 and CEACAM1 in metastasis CRC patients was much more than that in those CRC patients without metastasis. Herein, we propose to analyze the peripheral blood samples and primary/metastatic tumor lesions to reveal the expression differences of T cells in CRC with/without metastasis. Thus then we can set up a model for CRC prediction. And also, we will co-culture T cells and CRC cell line and utilize metastatic CRC mouse models to analyze the influence of TIM-3/CEACAM1 on the proliferation, metastasis and prognosis of CRC to find potential targets for the immunotherapy of metastatic CRC.