# Neurobiological pathways underlying brain tumor progression: basis for oncogenicity and opportunities for immunotherapeutic intervention

## TL;DR

This review explores how brain tumors interact with their environment and how these interactions could be targeted with immunotherapy.

## Contribution

The paper highlights novel immunotherapeutic opportunities by examining the role of tumor stem cells and the tumor microenvironment in brain tumor progression.

## Key findings

- Brain tumors integrate into synaptic networks and receive signals from the tumor microenvironment.
- Cancer stem cells play a key role in maintaining tumor progression and the tumor microenvironment.
- Targeting these mechanisms offers potential for new immunotherapies.

## Abstract

Both primary and metastatic brain tumors rely on signals from the surrounding environment for their survival and progression. In particular, the most common and lethal brain cancer, glioblastoma (GBM), derived from glial cells (astrocytes or microglia), has been shown to integrate into synaptic networks and to receive paracrine signals from neighbouring tumor microenvironment (TME) cells. There is increasing evidence that metastatic disease in the brain exhibits similar behavior. The TME both maintains malignant cells and is maintained by them, a process that relies on cancer stem cells (CSCs). These stem cells and their signaling mechanisms, including in the case of GBM, “GSCs,” provide possible novel targets for immunotherapy. In this review, we will discuss the integration of primary and malignant brain tumors into normal synaptic networks, the role of tumor stem cells and the TME in this integration, and the potential for immunotherapeutic targeting of these processes.