A Liquid Biopsy to Assess Brain Tumor Recurrence: Presence of Circulating Mo-MDSC and CD14+ VNN2+ Myeloid Cells as Biomarkers That Distinguish Brain Metastasis From Radiation Necrosis Following Stereotactic Radiosurgery.
A Liquid Biopsy to Assess Brain Tumor Recurrence: Presence of Circulating Mo-MDSC and CD14+ VNN2+ Myeloid Cells as Biomarkers That Distinguish Brain Metastasis From Radiation Necrosis Following Stereotactic Radiosurgery.
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DOI：
10.1093/neuros/nyaa334
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发表时间：
2020-08
期刊：
影响因子：
4.8
通讯作者：
D. Soler;Amber E. Kerstetter-Fogle;Theresa Elder;Alankrita Raghavan;J. Barnholtz-Sloan;K. Cooper;T. McCormick;A. Sloan
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文献类型：
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作者：
D. Soler;Amber E. Kerstetter-Fogle;Theresa Elder;Alankrita Raghavan;J. Barnholtz-Sloan;K. Cooper;T. McCormick;A. Sloan
背景脑转移瘤(BM)是美国最常见的脑肿瘤恶性肿瘤。它们也是立体定向放射外科(SRS)最常见的适应症。然而，随着治疗方法的改进，局部复发和放射性坏死(RN)的发生率都在增加。核磁共振成像通常不能区分BM和RN；因此，患者经常必须接受手术活检或切除才能获得明确的诊断。目的推测免疫抑制标志物可作为鉴别包括肾癌在内的活动性和非活动性肿瘤患者的替代标志物。方法采用流式细胞术对经活检证实为BM或RN患者的单核细胞髓系抑制细胞(Mo-MDSC)进行纯化和定量。结果我们报道了以前报道的人类白细胞抗原-DR-Vnn2指数(DVI)在利用外周血鉴别复发BM和RN方面的作用。脑转移复发患者外周血中CD14+HLA-DRneg/Low Mo-MDSC的比例明显高于RN患者(平均61.5%vs7%，n=10和n=12，P均<0.0001)。相反，BM患者外周血中CD14+单核细胞表面VNN2的表达低于RN患者(分别为5.5%和26.5%，n=10和n=12，P=.0008)。在活检证实脑转移瘤复发的患者中，平均DVI为11.65，而RN患者的平均DVI为1(Avg。0.17)。结论DVI可作为鉴别复发性BM和RN的一种有用的诊断工具。
BACKGROUND Brain metastases (BM) are the most common type of brain tumor malignancy in the US. They are also the most common indication for stereotactic radiosurgery (SRS). However, the incidence of both local recurrence and radiation necrosis (RN) is increasing as treatments improve. MRI imagery often fails to differentiate BM from RN; thus, patients must often undergo surgical biopsy or resection to obtain a definitive diagnosis. OBJECTIVE To hypothesize that a marker of immunosuppression might serve as a surrogate marker to differentiate patients with active vs inactive cancer-including RN. METHODS We thus purified and quantified Monocytic Myeloid-Derived Suppressor Cells (Mo-MDSC) by flow cytometry in patients proven by biopsy to represent BM or RN. RESULTS We report the utility of the previously reported HLA-Dr-Vnn2 Index or DVI to discriminate recurrent BM from RN using peripheral blood. The presence of CD14+ HLA-DRneg/low Mo-MDSC is significantly increased in the peripheral blood of patients with brain metastasis recurrence compared to RN (Average 61.5% vs 7%, n = 10 and n = 12, respectively, P < .0001). In contrast, expression of VNN2 on circulating CD14+ monocytes is decreased in BM patients compared to patients with RN (5.5% vs 26.5%, n = 10 and n = 12, respectively, P = .0008). In patients with biopsy confirmed recurrence of brain metastasis, the average DVI was 11.65, whereas the average DVI for RN patients was consistently <1 (Avg. of 0.17). CONCLUSION These results suggest that DVI could be a useful diagnostic tool to differentiate recurrent BM from RN using a minimally invasive blood sample.