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.
Highlights
Neuroblastoma is the most common extracranial childhood cancer and accounts for 8%-10% of all childhood cancers[1]
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
Summary
Neuroblastoma is the most common extracranial childhood cancer and accounts for 8%-10% of all childhood cancers[1]. It originates from neural crest progenitor cells and can occur anywhere along the sympathetic nervous system with the most common location being the adrenal glands[2,3]. Neuroblastoma can develop sporadically or display autosomal dominant inheritance. The latter occurs most commonly due to familial mutations in the ALK or PHOX2B genes[4,5]. The prognosis of neuroblastoma patients has improved in recent years[6]. The 5-year survival rate of patients with high-risk disease is still below 50%[2], highlighting the need for additional therapies
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