Department of Pediatrics, Georgia Health Sciences University, Augusta, Georgia 30912, USA.
Immunol Invest. 2012;41(6-7):765-97. doi: 10.3109/08820139.2012.689405.
Indoleamine 2,3-dioxygenase (IDO) is a natural mechanism of creating acquired tolerance in a variety of physiological settings. This endogenous tolerogenic pathway has important functions in regulating the magnitude of immune responses in settings of infection, pregnancy, tissue transplantation, mucosal interfaces and others. Whether for angiogenesis, stromal formation or immunologic tolerance, tumors often rely on recruiting host mechanisms. IDO is one such potent endogenous mechanism that appears to be frequently hijacked by tumors to establish systemic immune tolerance to tumor antigens. IDO can be expressed by tumors themselves, but, in addition, its natural site of expression is the host immune cells recruited by the tumor (particularly dendritic cells and macrophages). Therapeutic strategies that target the IDO pathway have been shown to synergize with standard chemotherapy and experimental immunotherapies to break tumor-induced tolerance. When such strategies target IDO expressed in host cells, they may be able to disrupt tolerance without creating intrinsic tumor cell drug resistance.
吲哚胺 2,3-双加氧酶 (IDO) 是在多种生理环境中产生获得性耐受的天然机制。这种内源性耐受途径在感染、妊娠、组织移植、黏膜界面等情况下调节免疫反应的强度方面具有重要作用。无论用于血管生成、基质形成还是免疫耐受，肿瘤通常都依赖于招募宿主机制。IDO 是一种强大的内源性机制，似乎经常被肿瘤劫持，以建立对肿瘤抗原的全身免疫耐受。IDO 可以由肿瘤本身表达，但除此之外，其天然表达部位是肿瘤募集的宿主免疫细胞（特别是树突状细胞和巨噬细胞）。靶向 IDO 途径的治疗策略已被证明与标准化疗和实验性免疫疗法协同作用，以打破肿瘤诱导的耐受。当此类策略针对宿主细胞中表达的 IDO 时，它们可能能够在不产生内在肿瘤细胞耐药性的情况下破坏耐受。
