Peripheral Neuroglia Forms the Inflammatory-Like Tumor Microenvironment

Various divisions of the nervous system can affect tumor growth and progression in vivo. However, far less is known about the mechanisms by which it is executed. Our program aims to investigate how the sensory division of the peripheral nervous system acts in the formation of the tumor microenvironment at the initial stage of carcinogenesis. Recently, we have reported sensory DRG (dorsal root ganglia) neurons to support tumor growth in vivo in experimental animal models. Our new data confirm these findings and provide new insights into the potential mechanisms of the phenomenon. We have found that melanoma-activated neuroglia expresses high levels of a pro-inflammatory S100A9 protein that attracts myeloid-derived suppressor cells (MDSC). Additionally, tumor-activated DRG neurons up-regulate expression of pro-nodal/nodal protein, known to induce polarization of conventional dendritic cells (DC) into tolerogenic regulatory DC. These data support the concept of the early interaction between initial malignant cells and the sensory (afferent) nervous system to result in the neuroglia-mediated formation of the inflammatory-like tolerogenic tumor immunoenvironment. Therefore, the cross-talk between cancerous, neuronal and immune cells plays a significant role in creating the unique tumor milieu resulting in antitumor immunity inhibition and tumor growth progression.