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B细胞浸润与神经母细胞瘤的预后及免疫浸润性肿瘤微环境高度相关。

B cell infiltration is highly associated with prognosis and an immune-infiltrated tumor microenvironment in neuroblastoma.

作者信息

Schaafsma Evelien, Jiang Chongming, Cheng Chao

机构信息

Department of Molecular and Systems Biology, Dartmouth College, Hanover, NH 03755, USA.

Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.

出版信息

J Cancer Metastasis Treat. 2021;7(34). doi: 10.20517/2394-4722.2021.72. Epub 2021 Jun 6.

Abstract

AIM

Neuroblastoma is the most common extracranial solid tumor in children. Recent advances in immunotherapy Approaches, including in neuroblastoma, have shown the important role of the immune system in mounting an effective anti-tumor response. In this study, we aimed to provide a comprehensive investigation of immune cell infiltration in neuroblastoma utilizing a large number of gene expression datasets.

METHODS

We inferred immune cell infiltration using an established immune inference method and evaluated the association between immune cell abundance and patient prognosis as well as common chromosomal abnormalities found in neuroblastoma. In addition, we evaluated co-infiltration patterns among distinct immune cell types.

RESULTS

The infiltration of naïve B cells, NK cells, and CD8+ T cells was associated with improved patient prognosis. Naïve B cells were the most consistent indicator of prognosis and associated with an active immune tumor microenvironment. Patients with high B cell infiltration showed high co-infiltration of other immune cell types and the enrichment of immune-related pathways. The presence of high B cell infiltration was associated with both recurrence-free and overall survival, even after adjusting for clinical variables.

CONCLUSION

In this study, we have provided a comprehensive evaluation of immune cell infiltration in neuroblastoma using gene expression data. We propose an important role for B cells in the neuroblastoma tumor microenvironment and suggest that B cells can be used as a prognostic biomarker to predict recurrence-free and overall survival independently of currently utilized prognostic variables.

摘要

目的

神经母细胞瘤是儿童最常见的颅外实体瘤。免疫治疗方法的最新进展,包括在神经母细胞瘤中的进展,已显示免疫系统在产生有效的抗肿瘤反应中发挥重要作用。在本研究中,我们旨在利用大量基因表达数据集对神经母细胞瘤中的免疫细胞浸润进行全面研究。

方法

我们使用既定的免疫推断方法推断免疫细胞浸润,并评估免疫细胞丰度与患者预后以及神经母细胞瘤中常见染色体异常之间的关联。此外,我们评估了不同免疫细胞类型之间的共浸润模式。

结果

幼稚B细胞、NK细胞和CD8+T细胞的浸润与患者预后改善相关。幼稚B细胞是最一致的预后指标,与活跃的免疫肿瘤微环境相关。B细胞浸润高的患者显示其他免疫细胞类型的共浸润高以及免疫相关途径的富集。即使在调整临床变量后,高B细胞浸润的存在与无复发生存率和总生存率均相关。

结论

在本研究中,我们利用基因表达数据对神经母细胞瘤中的免疫细胞浸润进行了全面评估。我们提出B细胞在神经母细胞瘤肿瘤微环境中起重要作用,并表明B细胞可作为一种预后生物标志物,独立于目前使用的预后变量来预测无复发生存率和总生存率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2977/8389852/329486e5d63a/nihms-1719673-f0001.jpg

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