Prognostic Significance of Tryptophan Catabolism in Adult T-cell Leukemia/Lymphoma
Prognostic Significance of Tryptophan Catabolism in Adult T-cell Leukemia/Lymphoma
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DOI：
10.1158/1078-0432.ccr-14-2275
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发表时间：
2015-06-15
影响因子：
11.5
通讯作者：
Iida, Shinsuke
中科院分区：
文献类型：
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作者：
Masaki, Ayako;Ishida, Takashi;Iida, Shinsuke
目的：吲哚胺2,3-双加氧酶1 （IDO1: IDO）是一种将色氨酸（Trp）分解为犬尿氨酸（Kyn）途径的酶，越来越被认为是抑制抗肿瘤免疫反应的重要微环境因子。本研究的目的是确定色氨酸分解代谢在成人t细胞白血病/淋巴瘤（ATL）中的预后意义。实验设计：我们对96例ATL患者、38例人类t细胞嗜淋巴病毒1型无症状携带者（HTLV-1 ACs）和40名健康成人志愿者的血清色氨酸和Kyn进行了定量分析。分析包括总生存期在内的各种临床参数之间的关系。评估ATL患者受影响淋巴结中IDO的表达。结果：HTLV-1 ACs患者血清Kyn浓度和Kyn/Trp比值显著高于健康对照组。随着HTLV-1 AC向ATL的进展，两者均显著升高。然而，ATL患者、HTLV-1 ACs和对照组之间的血清色氨酸浓度没有显著差异。IDO可能是由ATL和/或微环境细胞产生的。多因素分析表明，高血清Kyn/Trp比率和高Kyn水平，而不是高Trp水平，是ATL患者以及侵袭性变异型ATL患者预后的显著独立不利因素。结论：定量测定血清Kyn和Trp可用于预测ATL患者的预后。此外，ATL，特别是血清Kyn/Trp比值高的患者，是测试针对IDO的新型癌症免疫疗法的合适疾病。AACR (C) 2015。
Purpose: Indoleamine 2,3-dioxygenase 1 (IDO1: IDO), an enzyme catabolizing tryptophan (Trp) into the kynurenine (Kyn) pathway, is increasingly being recognized as an important micro-environmental factor suppressing antitumor immune responses. The purpose of the present study was to determine the prognostic significance of Trp catabolism in adult T-cell leukemia/lymphoma (ATL).Experimental Design: We quantified serum Trp and Kyn in 96 ATL patients, 38 human T-cell lymphotropic virus type-1 asymptomatic carriers (HTLV-1 ACs), and 40 healthy adult volunteer controls. The relationships between various clinical parameters including overall survival were analyzed. IDO expression was evaluated in the affected lymph nodes of ATL patients.Results: Serum Kyn concentrations and Kyn/Trp ratios were significantly higher in HTLV-1 ACs than healthy controls. Both increased significantly with progression from HTLV-1 AC to ATL. However, there were no significant differences in the serum Trp concentrations between ATL patients, HTLV-1 ACs, and controls. IDO was possibly produced by ATL and/or cells of the microenvironment. Multivariate analyses demonstrated that a high serum Kyn/Trp ratio and high Kyn level, but not a high Trp level, were significantly independent detrimental prognostic factors in ATL, as well as in that subset of patients with aggressive variant ATL.Conclusions: Quantification of serum Kyn and Trp is useful for predicting prognosis of an individual ATL patient. Furthermore, ATL, especially in patients with a high serum Kyn/Trp ratio, is an appropriate disease for testing novel cancer immunotherapies targeting IDO. (C)2015 AACR.