This independent and unbiased analysis shows that constitutive immune activation, including Interferon and NF-κB signaling together with a mesenchymal transcription program, is a common feature of cancer cells dependent on TAK1 function and therefore our mechanistic findings of a selective, targetable vulnerability in immune-activated glioma stem cells can be extended to many different cancer types. Here, NFKB1 is linked to central nervous system cancer.