Eosinophil granulocytes account for indoleamine 2,3-dioxygenase-mediated immune escape in human non-small cell lung cancer
Eosinophil granulocytes account for indoleamine 2,3-dioxygenase-mediated immune escape in human non-small cell lung cancer
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DOI：
10.1593/neo.04658
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发表时间：
2005-04-01
期刊：
影响因子：
4.8
通讯作者：
Frumento, G
中科院分区：
文献类型：
--
作者：
Astigiano, S;Morandi, B;Frumento, G
吲哚胺2，3-双加氧酶(IDO)是色氨酸的分解代谢酶，在肿瘤免疫逃逸中起重要作用。它在实体瘤中的表达还不清楚：IDO可以由肿瘤细胞本身表达，也可以由界限不清的浸润性细胞表达，可能取决于肿瘤的类型。我们研究了25例非小细胞肺癌(NSCLC)组织中IDO的表达。应用组织化学和免疫组织化学方法，我们发现IDO不是在肿瘤细胞中表达，而是在肿瘤周围基质中的正常细胞中表达。这些细胞既不是巨噬细胞，也不是树突状细胞，而是嗜酸性粒细胞。在不同的情况下，IDO阳性的嗜酸性粒细胞的数量不同，从几个细胞到200倍放大镜下每个视野50多个细胞不等。NSCLC中的IDO蛋白具有酶活性。因此，至少在非小细胞肺癌病例中，IDO阳性的嗜酸性粒细胞可以发挥有效的免疫抑制作用。对17例获得充分随访的患者进行分析，发现IDO阳性浸润物的数量与总存活率之间存在显著关系。这一发现提示IDO阳性的浸润性程度可能是NSCLC的一个预后标志。
Indoleamine 2,3-dioxygenase (IDO), a catabolizing enzyme of tryptophan, is supposed to play a role in tumor immune escape. Its expression in solid tumors has not yet been well elucidated: IDO can be expressed by the tumor cells themselves, or by ill-defined infiltrating cells, possibly depending on tumor type. We have investigated IDO expression in 25 cases of non-small cell lung cancer (NSCLC). Using histochemistry and immunohistochemistry, we found that IDO was expressed not by tumor cells, but by normal cells infiltrating the peritumoral stroma. These cells were neither macrophages nor dendritic cells, and were identified as eosinophil granulocytes. The amount of IDO-positive eosinophils varied in different cases, ranging from a few cells to more than 50 per field at x200 magnification. IDO protein in NSCLC was enzymatically active. Therefore, at least in NSCLC cases displaying a large amount of these cells in the inflammatory infiltrate, IDO-positive eosinophils could exert an effective immunosuppressive action. On analyzing the 17 patients with adequate follow-up, a significant relationship was found between the amount of IDO-positive infiltrate and overall survival. This finding suggests that the degree of IDO-positive infiltrate could be a prognostic marker in NSCLC.