Harnessing the innate immune system for glioblastoma therapeutics

Abstract

Glioblastoma is the most common primary malignant brain cancer and is associated with significant mortality and resistance to treatment. One of the major barriers to successful treatment of this cancer is the highly immunosuppressive tumour microenvironment. This tumour microenvironment is comprised of a complex mixture of cancerous cells, neurons, astrocytes, and a variety of immune cells. Microglia, macrophages and monocytes make up a significant proportion of the cells present in the glioblastoma tumour microenvironment. These innate immune cells normally act to maintain homeostasis, though following exposure to cancer cells are signalled to support glioblastoma cancer cell proliferation and treatment resistance. This review provides detailed insights into the role of innate immunity on glioblastoma cell proliferation and glioblastoma pathogenesis. It discusses ways of harnessing the anti-tumour potential of innate immune cells and documents the current preclinical and clinical trials focusing on innate immunity in glioblastoma. The work presented showcases how the anti-tumour capacity of innate immune cells could be utilised to provide novel treatment strategies to combat glioblastoma.