Li Fangxuan, Zhang Rupeng, Li Shixia, Liu Juntian
Department of Cancer Prevention Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; National Clinical Research Center for Cancer, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Tianjin's Clinical Research Center for Cancer, China.
Department of Gastric Cancer Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; National Clinical Research Center for Cancer, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Tianjin's Clinical Research Center for Cancer, China.
Int Immunopharmacol. 2017 Jun;47:70-77. doi: 10.1016/j.intimp.2017.03.024. Epub 2017 Mar 30.
Indoleamine 2,3-dioxigenase 1 (IDO1) acts in pathogenic inflammatory processes and engender immune tolerance to tumor antigens. IDO1 can decrease the tryptophan and produce a series of toxic kynurenine metabolites to promote the immune toleration via GCN2 pathway, mTOR pathway, toxic effect of kynurenine and favoring differentiation of Tregs. IDO1 can be induced in most human cells, especially APCs and cancer cells through canonical and non-canonical NF-κB and Jak/STAT pathways, as well as PKC and TGF-β signaling pathways. A series of human cancers over-express IDO1 in a constitutive way. Thus, IDO1 is likely to be an attractive target for developing inhibitors of tumor treatments. Many preclinical and clinical trials have been underway and suggest that IDO1 inhibitor maybe an effective tool against a wide range of cancers. However, the IDO1 inhibitor alone had been verified that to be disappointment in achieving effective antitumor efficacy. Concentrating on its molecular mechanism in immune toleration and complex environments of cancer, IDO1 inhibitor could cooperate with chemotherapies and other immune target inhibitors to lessen the tumor.
吲哚胺2,3-双加氧酶1（IDO1）在致病性炎症过程中发挥作用，并对肿瘤抗原产生免疫耐受。IDO1可降低色氨酸水平，并产生一系列有毒的犬尿氨酸代谢产物，通过GCN2途径、mTOR途径、犬尿氨酸的毒性作用以及促进调节性T细胞（Tregs）分化来促进免疫耐受。IDO1可在大多数人类细胞中被诱导，尤其是抗原呈递细胞（APCs）和癌细胞，通过经典和非经典的核因子κB（NF-κB）和Jak/STAT途径，以及蛋白激酶C（PKC）和转化生长因子-β（TGF-β）信号通路。一系列人类癌症以组成性方式过度表达IDO1。因此，IDO1可能是开发肿瘤治疗抑制剂的一个有吸引力的靶点。许多临床前和临床试验正在进行，表明IDO1抑制剂可能是对抗多种癌症的有效工具。然而，单独使用IDO1抑制剂已被证实，在实现有效的抗肿瘤疗效方面令人失望。鉴于其在免疫耐受和癌症复杂环境中的分子机制，IDO1抑制剂可与化疗和其他免疫靶点抑制剂联合使用，以减轻肿瘤。
