Yu Cheng-Peng, Song Yun-Lei, Zhu Zheng-Ming, Huang Bo, Xiao Ying-Qun, Luo Da-Ya
The Second Clinic Medical College, School of Medicine, Nanchang University, Nanchang, China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanchang University, Nanchang, China.
Med Oncol. 2017 May;34(5):73. doi: 10.1007/s12032-017-0933-2. Epub 2017 Mar 29.
Tryptophan-2,3-dioxygenase (TDO) is a homotetrameric heme-containing protein catalyzing the initial step in the kynurenine pathway, which oxidates the 2,3-double bond of the indole ring in L-tryptophan and catalyzes it into kynurenine (KYN). The upregulation of TDO results in a decrease in tryptophan and the accumulation of KYN and its metabolites. These metabolites can affect the proliferation of T cells. Increasing evidence demonstrates that TDO is a promising therapeutic target in the anti-tumor process. Despite its growing popularity, there are only a few reviews focusing on TDO in tumors. Hence, we herein review the biological features and regulatory mechanisms of TDO. Additionally, we focus on the role of TDO in the anti-tumor immune response in different tumors. Finally, we also provide our viewpoint regarding the future developmental directions of TDO in cancer research, especially in relation to the development and application of TDO inhibitors as novel cancer treatments.
色氨酸-2,3-双加氧酶（TDO）是一种含血红素的同四聚体蛋白，催化犬尿氨酸途径的第一步反应，该反应氧化L-色氨酸吲哚环的2,3-双键并将其催化生成犬尿氨酸（KYN）。TDO的上调导致色氨酸减少以及KYN及其代谢产物的积累。这些代谢产物可影响T细胞的增殖。越来越多的证据表明，TDO是抗肿瘤过程中有前景的治疗靶点。尽管其越来越受到关注，但仅有少数综述聚焦于肿瘤中的TDO。因此，我们在此综述TDO的生物学特性和调控机制。此外，我们关注TDO在不同肿瘤的抗肿瘤免疫反应中的作用。最后，我们还就TDO在癌症研究中的未来发展方向，特别是与作为新型癌症治疗方法的TDO抑制剂的开发和应用相关的方向，提出我们的观点。
