Clinical significance of tryptophan catabolism in follicular lymphoma
Clinical significance of tryptophan catabolism in follicular lymphoma
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DOI：
10.1002/hon.2804
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发表时间：
2020-09-29
影响因子：
3.3
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
吲哚胺 2,3-双加氧酶 1 (IDO) 酶可分解犬尿氨酸 (Kyn) 途径中的色氨酸 (Trp)，对于抑制肿瘤微环境中的抗肿瘤免疫反应非常重要。对于先前未经治疗的滤泡性淋巴瘤 (FL) 患者，我们试图确定色氨酸分解代谢在该疾病中的预后意义。对 110 名 FL 患者的血清 Trp 和 Kyn 水平进行了定量，并研究了它们与不同临床参数的关系。研究了受影响患者淋巴结中的 IDO 表达。研究参与者包括 54 名男性和 56 名女性（年龄范围 39-86 岁，中位年龄 62 岁），显示 5 年总生存 (OS) 率为 78.5%。具有高 Kyn 水平（5 年 OS，65.0% vs. 81.7%；p = 0.026）、高 Kyn/Trp 比值（71.1% vs. 81.7%；p = 0.002）和低血红蛋白 (Hb) 水平（p = 0.001；FL 国际预后指数的组成部分）的患者表现出显着较短的 OS。多变量分析包括以下10个变量：年龄、性别、血清β2-微球蛋白、Hb、最大受累淋巴结最长直径、Ann Arbor分期、血清乳酸脱氢酶、组织学分级、B症状和血清Kyn/Trp比值；较低的 Hb 水平和较高的 Kyn/Trp 比值（HR，3.239；95% CI，1.296-8.096）导致 OS 显着较差。在微环境中，一些 CD11c 阳性骨髓树突状细胞（而非 FL 肿瘤细胞）被发现产生 IDO。总体而言，测量个体 FL 患者的血清 Kyn 和 Trp 水平有助于预测其预后。
The enzyme, indoleamine 2,3-dioxygenase 1 (IDO), catabolizes tryptophan (Trp) in the kynurenine (Kyn) pathway, and is important in suppressing antitumor immune responses in the tumor microenvironment. With regard to previously untreated patients with follicular lymphoma (FL), we sought to establish the prognostic significance of Trp catabolism in this disease. Serum Trp and Kyn levels in 110 patients with FL were quantified, and their relationship to different clinical parameters studied. IDO expression in the lymph nodes of affected patients was studied. Study participants included 54 males and 56 females (age range 39-86, median 62 years), showing a 5-year overall survival (OS) rate of 78.5%. Patients with a high Kyn level (5-year OS, 65.0% vs. 81.7%;p = 0.026), high Kyn/Trp ratio (71.1% vs. 81.7%;p = 0.002), and low hemoglobin (Hb) level (p = 0.001; a component of FL international prognostic indexes) demonstrated a significantly shorter OS. Multivariate analysis included the following 10 variables: age, sex, serum beta 2-microglobulin, Hb, longest diameter of the largest involved node, Ann Arbor stage, serum lactate dehydrogenase, histologic grading, B symptoms, and serum Kyn/Trp ratio; a lower Hb level and a high Kyn/Trp ratio (HR, 3.239; 95% CI, 1.296-8.096) led to a significantly inferior OS. In the microenvironment, some CD11c-positive myeloid dendritic cells but not FL tumor cells were found to produce IDO. Overall, measuring levels of serum Kyn and Trp in individual patients with FL contributed to predicting their prognosis.