Pericytes in Glioblastomas: Multifaceted Role Within Tumor Microenvironments and Potential for Therapeutic Interventions.

Abstract

Glioblastoma (GBM) is an aggressive and lethal disease that often results in a poor prognosis. Unlike most solid tumors, GBM is characterized by diffuse infiltrating margins, extensive angiogenesis, hypoxia, necrosis, and clonal heterogeneity. Recurrent disease is an unavoidable consequence for many patients as standard treatment options such as surgery, radiotherapy, and chemotherapy have proven to be insufficient in causing long-term survival benefits. Systemic delivery of promising drugs is hindered due to the blood-brain barrier and non-uniform perfusion within GBM tissue. In recent years, many investigations have highlighted the role of GBM stem cells (GSCs) and their microenvironment in the initiation and maintenance of tumor tissue. Preclinical and early clinical studies to target GSCs and microenvironmental components are currently underway. Of these strategies, immunotherapy using checkpoint inhibitors and redirected cytotoxic T cells have shown promising results in early investigations. But, GBM microenvironment is heterogenous and recent investigations have shown cell populations within this microenvironment to be plastic. These studies underline the importance of identifying the role of and targeting multiple cell populations within the GBM microenvironment which could have a synergistic effect when combined with novel therapies. Pericytes are multipotent perivascular cells that play a vital role within the GBM microenvironment by assisting in tumor initiation, survival, and progression. Due to their role in regulating the blood-brain barrier permeability, promoting angiogenesis, tumor growth, clearing extracellular matrix for infiltrating GBM cells and in helping GBM cells evade immune surveillance, pericytes could be ideal therapeutic targets for stymieing or exploiting their role within the GBM microenvironment. This chapter will introduce hallmarks of GBM and elaborate on the contributions of pericytes to these hallmarks by examining recent findings. In addition, the chapter also highlights the therapeutic value of targeting pericytes, while discussing conventional and novel GBM therapies and obstacles to their efficacy.