Neuroblastoma Tumor Microenvironment: Non-Immune Cells and Exosomes

Schwann cells (SC), endothelial cells (EC), pericytes, and cancer-associated fibroblasts (CAF) are non-immune cells present in the tumor microenvironment (TME) of neuroblastoma (NB) tumors. These cells communicate with neuroblastoma (NB) cells through contact-dependent and contact-independent mechanisms which stimulate the production of soluble cytokines and chemokines that contribute to a pro-tumorigenic inflammatory reaction. Their roles in the TME of NB are substantially different and can be anti- as well as pro-tumorigenic. There is recent evidence that although these cells are not part of the immune system, they communicate with immune cells, modulating the immune response and often promoting immune escape. As our knowledge on the contribution of non-immune stromal cells in NB continues to expand, therapeutic approaches targeting these cells are considered. In this chapter, the role of SC, EC, and CAF, their mechanisms of communication with NB cells and immune cells, and recent clinical trials targeting these cells or their activity are reviewed in the context of recent literature.