Understanding the heterogeneous immune repertoire of brain metastases for designing next-gen therapeutics

Approximately 20% of cancer patients experience brain metastases in the advanced stages as circulating tumor cells migrate to and colonize the brain microvasculature. Due to the challenges associated with biopsies, our understanding of the tumor microenvironment and heterogeneity in brain metastases remains limited, hindering the development of systemic approaches for detection and treatment. Emerging evidence suggests that specific brain metastases induce a substantial level of immune activation and infiltration, which provides an opportunity to design specific immunotherapies targeting brain metastases. This perspective aims to summarize recent advancements in molecular profiling of the immune repertoires of brain metastases using biopsy-based approaches, with an emphasis on tumor-reactive T cells. Additionally, we discuss the potential of alternative tissues and technologies that offer improved temporal resolution, throughput, and fidelity for tracking tumor dynamics.