The molecular and immune microenvironmental landscape of brain metastases: Implications for novel treatment options

Brain metastases (BM), in which cells from a primary malignant tumor spread through the circulatory system into the microvasculature of the brain, eventually progress despite multiple therapeutic programmes and significantly lead to mortality in patients with advanced cancer. Unravelling the molecular features of the tumor microenvironment (TME) and immunological elements are emerging as key regulators of brain-specific metastases and establishment of efficacy. A comprehensive perspective on the molecular biology and immune landscape features contributing to the process of BM form will significantly broaden the horizon of therapeutic strategies available for deadly diseases. In this review, we provide a comprehensive picture of the complex interactions between tumor cells and cellular elements of the immune system involved in the BM process. Based on this knowledge, we will discuss opportunities and challenges for therapeutic strategies against BM.