Emerging principles of brain immunology and immune checkpoint blockade in brain metastases

Brain metastases are the most common type of brain tumours, harbouring an immune microenvironment that can in principle be targeted via immunotherapy. Elucidating some of the immunological intricacies of brain metastases has opened a therapeutic window to explore the potential of immune checkpoint inhibitors in this globally lethal disease. Multiple lines of evidence suggest that tumour cells hijack the immune regulatory mechanisms in the brain for the benefit of their own survival and progression. Nonetheless, the role of the immune checkpoint in the complex interplays between cancers cells and T cells and in conferring resistance to therapy remains under investigation. Meanwhile, early phase trials with immune checkpoint inhibitors have reported clinical benefit in patients with brain metastases from melanoma and non-small cell lung cancer. In this review, we explore the workings of the immune system in the brain, the immunology of brain metastases, and the current status of immune checkpoint inhibitors in the treatment of brain metastases.