Expression of indoleamine 2,3-dioxygenase in metastatic malignant melanoma recruits regulatory T cells to avoid immune detection and affects survival
Expression of indoleamine 2,3-dioxygenase in metastatic malignant melanoma recruits regulatory T cells to avoid immune detection and affects survival
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DOI：
10.4161/cc.8.12.8745
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发表时间：
2009-06-15
期刊：
影响因子：
4.3
通讯作者：
Witkiewicz, Agnieszka K.
中科院分区：
文献类型：
--
作者：
Brody, Jonathan R.;Costantino, Christina L.;Witkiewicz, Agnieszka K.
恶性黑色素瘤（MM）细胞在淋巴结中存活的机制知之甚少。MM细胞可以逃避免疫监视的一种可能机制是通过上调免疫调节酶如吲哚胺2，3-双加氧酶（IDO）。在这项研究中，25例MM淋巴结转移患者的长期和短期生存进行了评估IDO的表达和叉头盒p3（FOXP 3）表达的调节性T细胞的数量。中度至强胞质IDO表达存在于所有（15/15）生存不良患者的MM淋巴结转移灶中。10例转移性MM和长期生存的患者中有8例IDO阴性或仅弱阳性。转移性MM细胞中IDO的上调与调节性T细胞（TcB）数量的增加相关。在较短的生存期与较强的IDO表达（p = 0.0019）和较高数量的FOXP 3表达TcB（p < 0.001）之间存在统计学显著关联。使用RT-PCR分析，我们表明IDO在MM细胞中的表达由干扰素-γ诱导。这些数据支持转移性MM细胞选择表达IDO以逃避免疫学检测的观点。因此，在MM患者中抑制IDO可能是一种有用的治疗策略。
The mechanism by which malignant melanoma (MM) cells survive in lymph nodes is poorly understood. One possible mechanism by which MM cells can escape immune surveillance is through upregulation of immunomodulatory enzymes such as indoleamine 2,3-dioxygenase (IDO). In this study, 25 cases of MM lymph node metastases from patients with long and short survival were evaluated for expression of IDO and the number of Forkhead box p3 (FOXP3)-expressing regulatory T cells. Moderate to strong cytoplasmic IDO expression was present in all (15/15) MM lymph node metastases in patients with poor survival. Eight of 10 patients with metastatic MM and long survival were negative or only weakly positive for IDO. Upregulation of IDO in metastatic MM cells was associated with an increased number of regulatory T cells (Tregs). There was a statistically significant association between shorter survival and both a stronger IDO expression (p = 0.0019) and a higher number of FOXP3 expressing Tregs (p < 0.001). Using RT-PCR analysis, we showed that IDO expression in MM cells is induced by interferon-gamma. These data support the notion that metastatic MM cells select for expression of IDO to evade immunologic detection. Therefore, inhibition of IDO in MM patients may be a useful treatment strategy.