Interdependencies of the Neuronal, Immune and Tumor Microenvironment in Gliomas

SIMPLE SUMMARY: Gliomas are the most common primary brain tumors. These cancers are universally fatal with limited treatment options. Glioma cells co-opt non-cancerous cells present in normal brain tissue. This manipulation results in a complex network of cell interactions. This interplay is further complicated by variations depending on specific mutations in glioma cells. In order to identify future treatments for gliomas, a better understanding of these interactions is needed. To address this, we review the literature to highlight these interactions and how they relate to different glioma mutations. ABSTRACT: Gliomas are the most common primary brain malignancy and are universally fatal. Despite significant breakthrough in understanding tumor biology, treatment breakthroughs have been limited. There is a growing appreciation that major limitations on effective treatment are related to the unique and highly complex glioma tumor microenvironment (TME). The TME consists of multiple different cell types, broadly categorized into tumoral, immune and non-tumoral, non-immune cells. Each group provides significant influence on the others, generating a pro-tumor dynamic with significant immunosuppression. In addition, glioma cells are highly heterogenous with various molecular distinctions on the cellular level. These variations, in turn, lead to their own unique influence on the TME. To develop future treatments, an understanding of this complex TME interplay is needed. To this end, we describe the TME in adult gliomas through interactions between its various components and through various glioma molecular phenotypes.