新陈代谢改变在肿瘤细胞中很常见，这是它们适应可用的能量来源以促进其增殖、生存和抗性的方式。吲哚胺2,3-二氧化酶1 (IDO1) 是一种将色氨酸降解为骈酸的胞内酶。IDO1 表达在许多类型的人类癌肿瘤基质中上升，并为癌细胞逃避免疫监视提供了负反馈机制。IDO1 的上调与癌症侵袭、预后不良和患者生存时间缩短相关。这种内源性检查点的增加活性会损害效应 T 细胞功能，增加调节 T 细胞 (Treg) 人口，并诱导免疫耐受性。因此，IDO1 的抑制有助于增强抗肿瘤免疫反应，并通过归正效应 T 细胞活性来重新塑造肿瘤微环境 (TME) 的免疫状态。一个要点是，这种免疫调节标志物的表达在免疫检查点抑制剂 (ICI) 治疗后上调，并且它对其他检查点的表达具有诱导效应。这提示了 IDO1 作为一个有吸引力的免疫治疗靶点的重要性，并为在先进实体癌患者中合理组合 IDO1 抑制剂与 ICI 药物提供了合理化的依据。本文旨在讨论 IDO1 对肿瘤免疫生态系统的影响以及 IDO1 调节的 ICI 治疗绕过。同时，本文还关注 IDO1 抑制剂治疗与ICI 在晚期/转移性实体肿瘤中的疗效。 版权所有 © 2023 Elsevier B.V.

Metabolic alterations occur commonly in tumor cells as a way to adapt available energetic sources for their proliferation, survival and resistance. Indoleamine 2,3-dioxygenase 1 (IDO1) is an intracellular enzyme catalyzing tryptophan degradation into kynurenine. IDO1 expression shows a rise in the stroma of many types of human cancers, and it provides a negative feedback mechanism for cancer evasion from immunosurveillance. Upregulation of IDO1 correlates with cancer aggression, poor prognosis and shortened patient survival. The increased activity of this endogenous checkpoint impairs effector T cell function, increases regulatory T cell (Treg) population and induces immune tolerance, so its inhibition potentiates anti-tumor immune responses and reshapes immunogenic state of tumor microenvironment (TME) presumably through normalizing effector T cell activity. A point is that the expression of this immunoregulatory marker is upregulated after immune checkpoint inhibitor (ICI) therapy, and that it has inducible effect on expression of other checkpoints. These are indicative of the importance of IDO1 as an attractive immunotherapeutic target and rationalizing combination of IDO1 inhibitors with ICI drugs in patients with advanced solid cancers. In this review, we aimed to discuss about the impact of IDO1 on tumor immune ecosystem, and the IDO1-mediated bypass of ICI therapy. The efficacy of IDO1 inhibitor therapy in combination with ICIs in advanced/metastatic solid tumors is also a focus of this paper.Copyright © 2023 Elsevier B.V. All rights reserved.