The role of spatial transcriptomics in exploring the tumor microenvironment in neuroblastoma

Neuroblastoma is the most common extracranial solid tumor in children and exhibits significant variability in clinical outcomes. Our current understanding of the biology of neuroblastoma has been limited by an incomplete understanding of the complex interaction between tumor cells and the host cells within the tumor microenvironment (TME). The TME is composed of a rich ecosystem of immune and stromal cells, which may play a role in tumor establishment, growth, treatment resistance, and recurrence. Single-cell analysis platforms have been employed to characterize the tumor and non-tumor cells of the TME; however, many of these techniques require dissociation of the tissue into single-cell suspensions that sacrifice the critical spatial organization of the tumor. Spatial transcriptomics (ST) can be used to measure gene expression across a tissue sample with preserved native architecture. While older platforms were limited by their resolution, novel ST technologies now enable single-cell analysis and have the potential to revolutionize our understanding of the biology of the neuroblastoma TME. In this review, we will discuss the historical foundations of spatial biology, the application of single-cell technologies to neuroblastoma, and finally the groundbreaking implications of ST for the future study of neuroblastoma.