IDO与结肠癌的恶性程度及不良预后密切相关。IDO介导的低色氨酸环境，或其代谢产物犬尿氨酸等可促进Tregs增殖，髓系抑制细胞招募增多，IL-10和TGF-β分泌增加，维持免疫耐受环境。本课题组前期研究发现：在小鼠结肠癌模型中，IDO的表达与活性显著升高，而IDO-/-小鼠的成瘤率明显低于野生型小鼠；给予IDO抑制剂后，结肠部位的免疫耐受微环境得以逆转，结肠癌增殖受阻；提示IDO既参与调控T细胞的不平衡分化，也可通过免疫非依赖的途径直接调控肿瘤细胞增殖，其确切机制有待进一步研究。目前国内外对IDO在结肠癌中的调控作用及其抑制剂用于结肠癌化学预防鲜有报道。本项目拟运用IDO、Rag1、AhR等敲除小鼠模型，结合肿瘤细胞-T细胞共培养体外模型，深入研究IDO对T细胞分化及对肿瘤细胞增殖的调控作用和确切机制，找寻免疫调控干预结肠癌进程的有效途径，为非可控性炎症恶性转化的防治提供新思路。

Indoleamine 2,3-dioxygenase (IDO) is greatly involved in the development and progression of many cancer types. It was reported that IDO played a critical role in induction of immune escape. IDO activation was reported to correlate with poor clinical outcomes in patients with endometrial carcinoma, ovarian carcinoma and CRC. In the tumor microenvironment, kyn and other metabolites derived from tryptophan through IDO activation could suppress the proliferation of functional T cells and natural killer cells, but promote the differentiation and activation of Foxp3+ regulatory T cells. We demonstrated that kynurenine was required for IDO-mediated T cells function. Kyn promoted AhR nuclear translocation, and increased the transcription of Foxp3, through improving the interaction between AhR and Foxp3 promoter. Additionally, comparing to WT mice, IDO-/- mice treated with AOM/DSS exhibited fewer and smaller tumor burdens in colon, with fewer Tregs and more CD8+ T cells infiltration, while Kyn administration abolished this regulation. Rag1-/- mice, which lacked T cells, were sensitive to AOM/DSS-induced CRC, verifying that T cells-mediated adaptive immunity indeed played a critical role in CRC. We also demonstrated the chemopreventive effects of 1-L-MT on colitis-associated cancer, which were independent of adaptive immunity. IDO inhibition induced mitotic death, which was mediated by decreased Kyn production. The aim of this study is to investigate the role of IDO in the development of intestinal tumor induced by AOM/DSS, and illustrate the mechanisms of how IDO/Kyn/AhR pathway is involved in the progression of colorectal cancer. The result of this study would shed light on the prevention of the colorectal cancer.