Abstract

Indoleamine 2, 3-dioxygenase (IDO) as an intracellular cytosolic enzyme converts tryptophan (Trp) to N-formyl kynurenine which leads to proinflammatory T-cell apoptosis and prevention of immune cells maturation via decreasing the level of cellular energy. Trp catabolism products such as kynurenine increase the recruitment of regulatory T cells and induce immune tolerance in dendritic cells. IDO expression can locally suppress immunity in the tumor microenvironment and tumor progression actively recruits IDO expressing cells in tumor-draining lymph nodes. Also, tumor infiltrating Tregs’ activity leads to IDO expression in the tumor microenvironment. In this review, we described the immunomodulatory function of IDO and IDO-based therapeutic strategies for immune related diseases. According to positive-feedback loop between Tregs and IDO in the tumor microenvironment, IDO can be targeted as a promising immunostimulatory approach for immunotherapy of cancer. However, several studies revealed controversial consequences for influences of IDO in immunity. Considering the common concept, IDO1 and also IDO2 repress the function of T lymphocytes, while inactivation of IDO results in aggravation of some autoimmune diseases. Eventually, the extensive evaluation of IDO function in immunomodulatory procedure can help achieve IDO inhibitors as optimal drugs to inhibit tumor growth without motivating autoimmunity.

摘要

吲哚胺 2, 3-双加氧酶 (IDO) 作为细胞内胞质酶将色氨酸 (Trp) 转化为N-甲酰基犬尿氨酸，通过降低细胞能量水平导致促炎性 T 细胞凋亡和预防免疫细胞成熟。犬尿氨酸等色氨酸分解代谢产物可增加调节性 T 细胞的募集并诱导树突状细胞的免疫耐受。IDO 表达可以局部抑制肿瘤微环境中的免疫，并且肿瘤进展会在肿瘤引流淋巴结中主动招募 IDO 表达细胞。此外，肿瘤浸润性 Tregs 的活性导致 IDO 在肿瘤微环境中表达。在这篇综述中，我们描述了 IDO 的免疫调节功能和基于 IDO 的免疫相关疾病治疗策略。根据肿瘤微环境中Tregs和IDO之间的正反馈循环，IDO 可以作为一种有前途的免疫刺激方法用于癌症的免疫治疗。然而，一些研究揭示了 IDO 对免疫影响的争议性后果。考虑到共同的概念，IDO1和IDO2都会抑制T淋巴细胞的功能，而IDO的失活会导致一些自身免疫性疾病的恶化。最终，在免疫调节过程中对 IDO 功能的广泛评估可以帮助 IDO 抑制剂成为抑制肿瘤生长而不激发自身免疫的最佳药物。