Neuroblastoma reveals infiltration of T-cells and immunosuppressive macrophages: A meta-analysis on the neuroblastoma immune landscape

Abstract

Neuroblastoma is a common type of childhood cancer, with survival varying from over 90% in low-risk stages to less than 50% in high-risk patients. Especially in this high-risk group treatment resistance and relapse are common and the success of immune therapies so far has been lacking. In this meta-analysis, we aim to uncover the composition of the neuroblastoma immune landscape in order to get new insights into prognostic markers and possible therapeutic avenues. We compared results from IHC, scRNAseq, and snRNAseq methods and identified effector T-cells, and macrophages as the most abundant immune cell types present in neuroblastoma samples. Moreover, we observed a reduced number of lymphocytes upon MYCN amplification, whereas the myeloid fraction remained relatively similar. This myeloid lineage, especially the immunosuppressive macrophages, might provide a new and promising therapeutical target in high-risk neuroblastoma, as the T-cell pool showed signs of exhaustion. Additionally, we observed differences between sexes in the amount of immune infiltration. Therefore, sex may need to be considered when deciding on treatment regimes. In this review, we will discuss the data and limitations of IHC, and sc/snRNAseq methods, which are commonly used for determining immune infiltration and we will highlight the implications of the levels of immune infiltration and the presence of immunosuppressive populations on treatment strategy.