Yang Pengbo, Zhang Junhua
Department of Laboratory Medicine, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China.
The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing 100730, China.
Biomedicines. 2023 Jul 13;11(7):1988. doi: 10.3390/biomedicines11071988.
Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme enzyme involved in catalyzing the conversion of tryptophan (Trp) into kynurenine (Kyn) at the first rate-limiting step in the kynurenine pathway of L-tryptophan metabolism. It has been found to be involved in several biological functions such as aging, immune microorganism, neurodegenerative and infectious diseases, and cancer. IDO1 plays an important role in immune tolerance by depleting tryptophan in the tumor microenvironment and inhibiting the proliferation of effector T cells, which makes it an important emerging biomarker for cancer immunotherapy. Therefore, the research and development of IDO1 inhibitors are of great importance for tumor therapy. Of interest, IDO activity assays are of great value in the screening and evaluation of inhibitors. Herein, we mainly review the biological functions of IDO1, immune regulation, key signaling molecules in the response pathway, and the development of IDO1 inhibitors in clinical trials. Furthermore, this review provides a comprehensive overview and, in particular, a discussion of currently available IDO activity assays for use in the evaluation of IDO inhibitors in human blood. We believe that the IDO activity is a promising biomarker for the immune escape and laboratory evaluation of tumor immunotherapy.
吲哚胺2,3-双加氧酶1(IDO1)是一种血红素酶,参与在L-色氨酸代谢的犬尿氨酸途径的第一步限速步骤中催化色氨酸(Trp)转化为犬尿氨酸(Kyn)。已发现它参与多种生物学功能,如衰老、免疫微生物、神经退行性疾病和传染病以及癌症。IDO1通过消耗肿瘤微环境中的色氨酸并抑制效应T细胞的增殖在免疫耐受中发挥重要作用,这使其成为癌症免疫治疗中一个重要的新兴生物标志物。因此,IDO1抑制剂的研发对肿瘤治疗具有重要意义。有趣的是,IDO活性测定在抑制剂的筛选和评估中具有重要价值。在此,我们主要综述IDO1的生物学功能、免疫调节、反应途径中的关键信号分子以及IDO1抑制剂在临床试验中的进展。此外,本综述提供了全面的概述,特别是对目前可用于评估人血中IDO抑制剂的IDO活性测定方法的讨论。我们认为,IDO活性是肿瘤免疫治疗免疫逃逸和实验室评估的一个有前景的生物标志物。