More than the genes, the tumor microenvironment in neuroblastoma

Abstract

Neuroblastoma is the second most common solid tumor in children. Since the seminal discovery of the role of amplification of the MYCN oncogene in the pathogenesis of neuroblastoma in the 1980s, much focus has been on the contribution of genetic alterations in the progression of this cancer. However it is now clear that not only genetic events play a role but that the tumor microenvironment (TME) substantially contributes to the biology of neuroblastoma. In this article, we present a comprehensive review of the literature on the contribution of the TME to the ten hallmarks of cancer in neuroblastoma and discuss the mechanisms of communication between neuroblastoma cells and the TME that underlie the influence of the TME on neuroblastoma progression. We end our review by discussing how the knowledge acquired over the last two decades in this field is now leading to new clinical trials targeting the TME.

Keywords: Cell–cell communication; Hallmarks of cancer; Neuroblastoma; Tumor microenvironment.

Fig. 1

Diagram summarizing the contribution of the cells and ECM in the TME to the ten hallmarks of cancer shown at the center of the wheel. The central graph was reproduced from Hanahan and Weinberg [15].

Fig. 2

Diagram summarizing the major mechanisms of communication between neuroblastoma cells and TME cells and the ECM and pathways they activate in neuroblastoma cells.