Astrocyte-driven immunosuppression in the brain tumor microenvironment

Brain tumors are among the most lethal cancers, with limited success from emerging immunotherapies, largely due to the reshaping of the surrounding tumor microenvironment to promote tumor growth, invasion and immune evasion. Astrocytes are abundant glial cells of the central nervous system (CNS) that can activate distinct molecular programs to support glioblastoma and brain metastases. Although astrocytes are central regulators of the immune response in the CNS, their role in shaping tumor immunity remains relatively underexplored. Emerging evidence indicates that reactive astrocytes are important drivers of local immunosuppression, which constitutes a major barrier to the development of efficacious immunotherapies for brain tumors. In this Review, we examine astrocyte reprogramming by tumor-derived signals, its effect on tumor immunity, and emerging strategies to modulate astrocyte responses and immunotherapy outcomes.