Department of Immunology, Hebei Medical University, Shijiazhuang, China.
Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, China.
Front Immunol. 2021 Dec 23;12:800630. doi: 10.3389/fimmu.2021.800630. eCollection 2021.
Tumorigenesis is a complex multifactorial and multistep process in which tumors can utilize a diverse repertoire of immunosuppressive mechanisms to evade host immune attacks. The degradation of tryptophan into immunosuppressive kynurenine is considered an important immunosuppressive mechanism in the tumor microenvironment. There are three enzymes, namely, tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase 1 (IDO1), and indoleamine 2,3-dioxygenase 2 (IDO2), involved in the metabolism of tryptophan. IDO1 has a wider distribution and higher activity in catalyzing tryptophan than the other two; therefore, it has been studied most extensively. IDO1 is a cytosolic monomeric, heme-containing enzyme, which is now considered an authentic immune regulator and represents one of the promising drug targets for tumor immunotherapy. Collectively, this review highlights the regulation of IDO1 gene expression and the ambivalent mechanisms of IDO1 on the antitumoral immune response. Further, new therapeutic targets the regulation of IDO1 are discussed. A comprehensive analysis of the expression and biological function of IDO1 can help us to understand the therapeutic strategies of the inhibitors targeting IDO1 in malignant tumors.
肿瘤发生是一个复杂的多因素、多步骤的过程，肿瘤可以利用多种免疫抑制机制来逃避宿主的免疫攻击。色氨酸降解为免疫抑制性犬尿氨酸被认为是肿瘤微环境中的一种重要免疫抑制机制。有三种酶参与色氨酸的代谢，即色氨酸 2,3-双加氧酶（TDO）、吲哚胺 2,3-双加氧酶 1（IDO1）和吲哚胺 2,3-双加氧酶 2（IDO2）。IDO1 在催化色氨酸方面的分布更广，活性更高；因此，它被研究得最多。IDO1 是一种胞质单体、血红素结合酶，现在被认为是一种真正的免疫调节剂，是肿瘤免疫治疗有前途的药物靶点之一。综上所述，本综述强调了 IDO1 基因表达的调控以及 IDO1 对抗肿瘤免疫反应的双重作用机制。此外，还讨论了新的治疗靶点——IDO1 的调控。对 IDO1 的表达和生物学功能进行全面分析，有助于我们理解针对 IDO1 的抑制剂在恶性肿瘤中的治疗策略。
