The Role of Microglia in Brain Metastases: Mechanisms and Strategies

Abstract

Brain metastases and related complications are one of the major fatal factors in cancer. Patients with breast cancer, lung cancer, and melanoma are at a high risk of developing brain metastases. However, the mechanisms underlying the brain metastatic cascade remain poorly understood. Microglia, one of the major resident macrophages in the brain parenchyma, are involved in multiple processes associated with brain metastasis, including inflammation, angiogenesis, and immune modulation. They also closely interact with metastatic cancer cells, astrocytes, and other immune cells. Current therapeutic approaches against metastatic brain cancers, including small-molecule drugs, antibody-coupled drugs (ADCs), and immune-checkpoint inhibitors (ICIs), have compromised efficacy owing to the impermeability of the blood-brain barrier (BBB) and complex brain microenvironment. Targeting microglia is one of the strategies for treating metastatic brain cancer. In this review, we summarize the multifaceted roles of microglia in brain metastases and highlight them as potential targets for future therapeutic interventions.

The Interplay between Glioblastoma Cells and Tumor Microenvironment: New Perspectives for Early Diagnosis and Targeted Cancer Therapy

“…During cancer progression, microglia cells polarize in different phenotypes: the M1 phenotype induces reactive oxygen species (ROS) and nitric oxide (NO) and releases proinflammatory cytokines (IL-1 β, IL-6, TNF α, CCL2), resulting in anti-tumor effects [46][47][48]; the M2 phenotype regulates anti-inflammatory cytokine secretion (TGF-β and IL-10) as well as immunosuppressive factors (ARG-1 and CD36), leading to pro-tumor consequences [49][50][51]. Several studies have demonstrated that glioma-associated microglia show both phenotypes in human GBM specimens, and distinguishing between these two phenotypes is very difficult [52,53].…”