Immunosuppressive cells in oncolytic virotherapy for glioma: challenges and solutions

Abstract

Glioblastoma is a highly aggressive form of brain cancer characterized by the abundance of myeloid lineage cells in the tumor microenvironment. Tumor-associated macrophages and microglia (TAM) and myeloid-derived suppressor cells (MDSCs), play a pivotal role in promoting immune suppression and tumor progression. Oncolytic viruses (OVs) are self-amplifying cytotoxic agents that can stimulate local anti-tumor immune responses and have the potential to suppress immunosuppressive myeloid cells and recruit tumor-infiltrating T lymphocytes (TILs) to the tumor site, leading to an adaptive immune response against tumors. However, the impact of OV therapy on the tumor-resident myeloid population and the subsequent immune responses are not yet fully understood. This review provides an overview of how TAM and MDSC respond to different types of OVs, and combination therapeutics that target the myeloid population to promote anti-tumor immune responses in the glioma microenvironment.

Keywords: MDSCs; glioblastoma; glioma; immunosuppressive; macrophages; microglia; oncolytic virus; tumor microenvironment.