Tumor Immune Microenvironment of Brain Metastases: Toward Unlocking Antitumor Immunity

Abstract Brain metastasis (BrM) is a devastating complication of solid tumors associated with poor outcomes. Immune-checkpoint inhibitors (ICI) have revolutionized the treatment of cancer, but determinants of response are incompletely understood. Given the rising incidence of BrM, improved understanding of immunobiologic principles unique to the central nervous system (CNS) and dissection of those that govern the activity of ICIs are paramount toward unlocking BrM-specific antitumor immunity. In this review, we seek to discuss the current clinical landscape of ICI activity in the CNS and CNS immunobiology, and we focus, in particular, on the role of glial cells in the CNS immune response to BrM. Significance: There is an urgent need to improve patient selection for and clinical activity of ICIs in patients with cancer with concomitant BrM. Increased understanding of the unique immunobiologic principles that govern response to ICIs in the CNS is critical toward identifying targets in the tumor microenvironment that may potentiate antitumor immunity.