吲哚胺2,3-双加氧酶1在结直肠癌中的研究进展

Research progress of indoleamine 2,3-dioxygenase 1 in colorectal cancer

结直肠癌(colorectal cancer,CRC)是世界第三大最常见的癌症,也是导致癌症相关死亡的第二大原因。目前,免疫治疗仅限于错配修复缺陷(mismatch repair deficient,dMMR)/微卫星高度不稳定(microsatellite instability-high,MSI-H)CRC的特定基因亚群。吲哚胺2,3-双加氧酶1(indoleamine 2,3-dioxygenase 1,IDO1)是参与色氨酸分解代谢的酶,在肿瘤微环境中具有中枢免疫抑制作用。IDO1在CRC中的高表达是影响整体生存和CRC转移的独立不良预后因素。目前,已有临床试验对几种IDO1抑制剂进行了评估,显示出良好的药代动力学特征和疗效。该文阐述了CRC的分子和免疫环境、IDO1在CRC中的表达及作用机制,并介绍了IDO1抑制剂在CRC中的临床研究进展。

Colorectal cancer(CRC)is the third most common cancer in the world which is the second leading cause of cancer-related deaths.Currently,immunotherapy is limited to specific gene subsets in mismatch repair deficient(dMMR)/microsatellite instability-high(MSI-H)colorectal cancer.Indoleamine 2,3-dioxygenase 1(IDO1)is an enzyme involved in tryptophan catabolism which has central immunosuppression effect in tumor microenvironment.High expression of IDO1 is an independent adverse prognostic factor of overall survival and metastasis of colorectal cancer.At present,several IDO1 inhibitors have been evaluated in clinical trials which show good pharmacokinetic characteristics and efficacy.In this paper,the molecular and immune environment of colorectal cancer,the expression and mechanism of IDO1 in colorectal cancer and the clinical research progress of IDO1 inhibitors in colorectal cancer will be reviewed in this article.