Global immune fingerprinting in glioblastoma patient peripheral blood reveals immune-suppression signatures associated with prognosis
Global immune fingerprinting in glioblastoma patient peripheral blood reveals immune-suppression signatures associated with prognosis
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DOI：
10.1172/jci.insight.122264
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发表时间：
2018-11-02
期刊：
影响因子：
8
通讯作者：
Lathia, Justin D.
中科院分区：
文献类型：
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作者：
Alban, Tyler J.;Alvarado, Alvaro G.;Lathia, Justin D.
胶质母细胞瘤(GBM)具有一致的致死性，尽管微环境中有大量的免疫细胞聚集，但抗肿瘤免疫反应有限。为了克服这些挑战，需要全面了解疾病进展过程中的GBM系统免疫反应。在这里，我们结合了多参数流式细胞术和质量细胞术TOF(CyTOF)分析患者的血液，以确定肿瘤类型和疾病进展期间免疫系统的变化。利用流式细胞术对259例从良性到恶性的原发和转移性脑肿瘤患者进行分析，我们发现GBM患者外周血中髓系来源的抑制细胞(MDSCs)显著增加，但免疫抑制Tregs无明显变化。在GBM患者组织中，我们发现复发的GBM患者MDSC水平升高预示着不良预后。对新诊断的GBM患者的外周血进行的细胞TOF分析显示，随着时间的推移，MDSCs减少伴随着DC的增加。存活时间延长的GBM患者的MDSCs也减少，与低级别胶质瘤(LGG)患者的水平相似。我们的发现为制定针对MDSCs的策略提供了理论基础，MDSCs在GBM患者中升高，并预测不良的预后。
Glioblastoma (GBM) remains uniformly lethal, and despite a large accumulation of immune cells in the microenvironment, there is limited antitumor immune response. To overcome these challenges, a comprehensive understanding of GBM systemic immune response during disease progression is required. Here, we integrated multiparameter flow cytometry and mass cytometry TOF (CyTOF) analysis of patient blood to determine changes in the immune system among tumor types and over disease progression. Utilizing flow cytometry analysis in a cohort of 259 patients ranging from benign to malignant primary and metastatic brain tumors, we found that GBM patients had a significant elevation in myeloid-derived suppressor cells (MDSCs) in peripheral blood but not immunosuppressive Tregs. In GBM patient tissue, we found that increased MDSC levels in recurrent GBM portended poor prognosis. CyTOF analysis of peripheral blood from newly diagnosed GBM patients revealed that reduced MDSCs over time were accompanied by a concomitant increase in DCs. GBM patients with extended survival also had reduced MDSCs, similar to the levels of low-grade glioma (LGG) patients. Our findings provide a rationale for developing strategies to target MDSCs, which are elevated in GBM patients and predict poor prognosis.