Studies reveal critical immune mechanisms influencing cancers in the central nervous system and glioblastoma. Hernandez-Barranco and Joyce identified interferon-gamma-activated dendritic cells enforcing immune checkpoints against brain leptomeningeal metastases. Separately, viral barcode tracing exposed astrocyte-glioma crosstalk suppressing glioblastoma progression by mapping cell-to-cell signaling within tumor microenvironments. These insights open novel therapeutic avenues targeting immune components to enhance anti-tumor immunity and overcome resistance in aggressive brain cancers.