Revisiting glioblastoma classification through an immunological lens: A narrative review

Abstract

Glioblastoma (GBM) is characterized by a high recurrence rate, significant heterogeneity, and poor prognosis. While there has been a shift in recent years to focus on molecular phenotyping, there are limited data regarding the relationship between the immune milieu and heterogeneous molecular signatures in GBM. Given the success of immunotherapies in other cancers such as non-small-cell lung cancer and melanoma, there has been a concerted effort to correlate the immune compartment of the GBM tumor microenvironment to clinical outcomes. The aim of this narrative review is to establish the role of immunophenotyping in GBM classification. Major immune cell groups in GBM involve myeloid cells (e.g. myeloid-derived suppressor cells, tumor-associated macrophages and microglia, neutrophils, and dendritic cells), lymphocytes (e.g., T, natural killer, and B-cells), and stromal cells (e.g., fibroblasts, pericytes, and endothelial cells). Understanding the relationships between these different immune cell populations and correlating their roles with the current molecular classification scheme as described in the 2021 World Health Organization criteria may further elucidate patterns of clinical response, especially in light of recent advances in new immunotherapies.

Keywords

• classification
• glioblastoma
• immunophenotype
• immunotherapy
• lymphocytes
• myeloid cells
• review
• tumor microenvironment