IDO1 活性的动态变化可预测不可切除的 III 期 NSCLC 患者放化疗后的生存情况。
Dynamic change of IDO1 activity predicts survival in patients with unresectable stage III NSCLC and chemoradiotherapy.
机构信息
Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
出版信息
Front Immunol. 2022 Aug 10;13:906815. doi: 10.3389/fimmu.2022.906815. eCollection 2022.
OBJECTIVE
High activity of Indoleamine 2,3-dioxygenase1 (IDO1) in lung cancer patients converts tryptophan (Trp), which is the essential amino acid for T-cell metabolism, to kynurenine (Kyn) and consequently suppresses anti-tumor immune responses. We aimed to track the dynamics of IDO1 activity in stage III non-small cell lung cancer (NSCLC) patients who received first-line radiotherapy (RT) and explore its association with survival outcomes.
MATERIALS AND METHODS
Systemic IDO1 activity was calculated by Kyn : Trp ratio. Plasma levels of Kyn and Trp in 113 thoracic RT-received stage III NSCLC patients were measured by high-performance liquid chromatography before the initiation of RT. The dynamic change of IDO1 activity was followed in 24 patients by measuring the Kyn : Trp ratio before, during, and after RT administration.
RESULTS
In 24 patients with dynamic tracking of plasma IDO1 activity, there were no significant alterations observed among the three time points (Friedman test, p = 0.13). The changing pattern of the Kyn : Trp ratio was divided into four groups: decreased consistently during RT, first increased, then decreased, increased consistently, first decreased then increased. Patients whose Kyn : Trp ratio kept decreasing or first increased then decreased were defined as the good-change group. The good-change status was identified as an independent positive factor for overall survival (OS) and progression-free survival (PFS) (p = 0.04; p = 0.01) in multivariate analysis among evaluated parameters. Patients with good change showed significantly superior local control than the bad-change group (p = 0.01, HR = 0.22). In 113 stage III NSCLC patients with pre-radiation Kyn : Trp ratio, a trend that high baseline IDO1 activity was associated with short OS was observed (p = 0.079).
CONCLUSION
Favorable change in IDO1 activity during RT was associated with superior OS, PFS, and local control. IDO1 activity is a promising biomarker for prognosis in stage III NSCLC patients.
目的
肺癌患者中吲哚胺 2,3-双加氧酶 1（IDO1）的高活性将色氨酸（Trp），即 T 细胞代谢所必需的氨基酸，转化为犬尿氨酸（Kyn），从而抑制抗肿瘤免疫反应。我们旨在追踪接受一线放疗（RT）的 III 期非小细胞肺癌（NSCLC）患者 IDO1 活性的动态变化，并探讨其与生存结局的关系。
材料和方法
通过 Kyn：Trp 比值计算系统 IDO1 活性。在开始 RT 前，通过高效液相色谱法测量 113 名接受胸部 RT 的 III 期 NSCLC 患者的血浆中 Kyn 和 Trp 水平。通过在 RT 期间和之后测量 Kyn：Trp 比值，对 24 名患者进行了 IDO1 活性的动态跟踪。
结果
在 24 名具有血浆 IDO1 活性动态跟踪的患者中，三个时间点之间没有观察到显著变化（Friedman 检验，p = 0.13）。Kyn：Trp 比值的变化模式分为四组：在 RT 期间持续降低，先升高后降低，持续升高，先降低后升高。Kyn：Trp 比值持续降低或先升高后降低的患者被定义为良好变化组。在多因素分析中，良好变化状态被确定为总生存（OS）和无进展生存（PFS）的独立正因素（p = 0.04；p = 0.01）。与不良变化组相比，变化良好的患者局部控制明显更好（p = 0.01，HR = 0.22）。在 113 名接受放疗前 Kyn：Trp 比值的 III 期 NSCLC 患者中，观察到高基线 IDO1 活性与 OS 较短相关的趋势（p = 0.079）。
结论
RT 期间 IDO1 活性的良好变化与 OS、PFS 和局部控制更好相关。IDO1 活性是 III 期 NSCLC 患者预后的有前途的生物标志物。
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