Indoleamine 2,3-dioxygenase activity and clinical outcome following induction chemotherapy and concurrent chemoradiation in Stage III non-small cell lung cancer.
Indoleamine 2,3-dioxygenase activity and clinical outcome following induction chemotherapy and concurrent chemoradiation in Stage III non-small cell lung cancer.
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DOI：
10.4161/onci.23428
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发表时间：
2013-03-01
期刊：
影响因子：
7.2
通讯作者：
Soliman HH
中科院分区：
文献类型：
--
作者：
Creelan BC;Antonia S;Bepler G;Garrett TJ;Simon GR;Soliman HH
吲哚胺2，3-双加氧酶（IDO）最近被提出通过影响色氨酸（Trp）转化为犬尿氨酸（Kyn）来解释肿瘤诱导的免疫抑制。我们研究的目的是将IDO活性与用多模式组合疗法治疗的非小细胞肺癌（NSCLC）患者的疾病结果相关联。在一项涉及吉西他滨和卡铂诱导治疗，随后同时接受紫杉醇、卡铂和74戈伊胸部放疗的III期NSCLC患者的单组II期试验中，在基线、诱导后和同时治疗后采集血浆。平均血浆Kyn/Trp比值用作IDO活性的替代指标。33例受试者分布如下：15例女性，18例男性;中位年龄= 62岁;中位总生存期（OS）= 22.4（95% CI 19.3-25.1）个月;中位无进展生存期（PFS）= 11.5（95% CI 6.7-16.3）个月。基线时的平均Kyn/Trp比值（4.5 ± 2.8）高于健康对照组（2.9 ± 1.9，p = 0.03），诱导治疗（5.2 ± 3.2，p = 0.08）和放化疗（5.8 ± 3.9，p = 0.01）后增加。治疗后Kyn/Trp比值和放射学反应在任何时间点均无显著相关性。基线Kyn/Trp比值与OS（HR = 1.1，95% CI 0.45-2.5）或PFS（HR = 0.74，95% CI 0.30-1.82）之间无显著相关性。诱导化疗后IDO活性增加预示OS（HR = 0.43，95% CI 0.19-0.95，p = 0.037）和PFS（HR = 0.47，95% CI 0.22-1.0，p = 0.055）更差。这种观察到的IDO转录的增加可能是肿瘤逃避免疫监视的手段。
Indoleamine 2,3-dioxygenase (IDO) has recently been proposed to account for tumor-induced immunosuppression by influencing the conversion of tryptophan (Trp) into kynurenine (Kyn). The objective of our study was to correlate IDO activity with disease outcome in non-small cell lung cancer (NSCLC) patients treated with multimodal combination therapy. In a single-arm Phase II trial involving induction gemcitabine and carboplatin followed by concurrent paclitaxel, carboplatin and 74 Gy thoracic radiation in stage III NSCLC patients, plasma was drawn at baseline, post-induction, and post-concurrent therapy. The mean plasma Kyn/Trp ratio was used as a surrogate indicator of IDO activity. The 33 participants were distributed as follows: 15 females, 18 males; median age = 62; median overall survival (OS) = 22.4 (95% CI 19.3–25.1) months; median progression-free survival (PFS) = 11.5 (95% CI 6.7–16.3) months. The mean Kyn/Trp ratio at baseline (4.5 ± 2.8) was higher than that of healthy controls (2.9 ± 1.9, p = 0.03) and increased after induction therapy (5.2 ± 3.2, p = 0.08) and chemoradiation (5.8 ± 3.9, p = 0.01). The post-treatment Kyn/Trp ratio and radiologic responses were not significantly associated at any time point. No significant correlation was found between baseline Kyn/Trp ratios and OS (HR = 1.1, 95% CI 0.45–2.5) or PFS (HR = 0.74, 95% CI 0.30–1.82). A post-induction chemotherapy increase in IDO activity portended worse OS (HR = 0.43, 95% CI 0.19–0.95, p = 0.037) and PFS (HR = 0.47, 95% CI 0.22–1.0, p = 0.055). This observed increase in IDO transcription may be a means for tumors to evade immunosurveillance.
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影响因子：
1.3
作者：
Dharnidharka VR;Gupta S;Al Khasawneh E;Haafiz A;Shuster JJ;Theriaque DW;Shahlaee AH;Garrett TJ
通讯作者：
Garrett TJ
影响因子：
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影响因子：
4.8
作者：
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影响因子：
11.5
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影响因子：
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作者：
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