Asghar Kashif, Farooq Asim, Zulfiqar Bilal, Rashid Muhammad Usman
Kashif Asghar, Asim Farooq, Muhammad Usman Rashid, Department of Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore 54000, Pakistan.
World J Gastroenterol. 2017 Apr 7;23(13):2286-2293. doi: 10.3748/wjg.v23.i13.2286.
Tumor cells induce an immunosuppressive microenvironment which leads towards tumor immune escape. Understanding the intricacy of immunomodulation by tumor cells is essential for immunotherapy. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme which mediates tumor immune escape in various cancers including hepatocellular carcinoma (HCC). IDO up-regulation in HCC may lead to recruitment of regulatory T-cells into tumor microenvironment and therefore inhibit local immune responses and promote metastasis. HCC associated fibroblasts stimulate natural killer cells dysfunction through prostaglandin E2 and subsequently IDO promotes favorable condition for tumor metastasis. IDO up-regulation induces immunosuppression and may enhance the risk of hepatitis C virus and hepatitis B virus induced HCC. Therefore, IDO inhibitors as adjuvant therapeutic agents may have clinical implications in HCC. This review proposes future prospects of IDO not only as a therapeutic target but also as a prognostic marker for HCC.
肿瘤细胞诱导免疫抑制微环境，导致肿瘤免疫逃逸。了解肿瘤细胞免疫调节的复杂性对免疫治疗至关重要。吲哚胺2,3-双加氧酶（IDO）是一种免疫抑制酶，介导包括肝细胞癌（HCC）在内的多种癌症的肿瘤免疫逃逸。HCC中IDO上调可能导致调节性T细胞募集到肿瘤微环境中，从而抑制局部免疫反应并促进转移。HCC相关成纤维细胞通过前列腺素E2刺激自然杀伤细胞功能障碍，随后IDO为肿瘤转移创造有利条件。IDO上调诱导免疫抑制，并可能增加丙型肝炎病毒和乙型肝炎病毒诱导的HCC风险。因此，IDO抑制剂作为辅助治疗药物可能对HCC具有临床意义。本综述提出了IDO不仅作为治疗靶点，而且作为HCC预后标志物的未来前景。
