A Blazing Landscape: Neuroinflammation Shapes Brain Metastasis

Abstract

Brain metastases are more common than primary CNS tumors and confer grave prognosis on patients, as existing treatments have very limited efficacy. The tumor microenvironment has a central role in facilitating tumorigenesis and metastasis. In recent years, there has been much progress in our understanding of the functional role of the brain metastatic microenvironment. In this review, we discuss the latest advances in brain metastasis research, with special emphasis on the role of the brain microenvironment and neuroinflammation, integrating insights from comparable findings in neuropathologies and primary CNS tumors. In addition, we overview findings on the formation of a hospitable metastatic niche and point out the major gaps in knowledge toward developing new therapeutics that will cotarget the stromal compartment in an effort to improve the treatment and prevention of brain metastases.

Figure 1

A. Epidemiology of brain metastases. Summary of main epidemiological findings from various primary tumor types that metastasize to brain (%: percentage of brain metastasis cases diagnosed, m=months) (,,–172). B. The brain microenvironment: Illustration of different cell types in normal brain. The physiological roles of different brain cells are detailed in Box 1.

Figure 2

Reciprocal interactions between brain-metastasizing tumor cells and the brain microenvironment facilitate metastatic growth. Main findings of neuroinflammatory networks operative in brain metastasis.