Gene expression profiling of human glioblastoma cell lines treated with 8-Azaadenosine
Glioblastomas are the most frequent and aggressive primary brain tumors. Current treatments invariably fail, a consequence of the pronounced heterogeneity and plasticity of glioblastoma cells, as well as the contribution of an immunosuppressive microenvironment that promotes tumor progression and resistance to therapy. Here, we exploited an innate immunity checkpoint, RNA sensing, to simultaneously target cancer cells and their supporting microenvironment. Using various immunocompetent mouse models of glioblastoma, we found that genetic deletion of Adar1, a key regulator of the RNA sensing pathway, resulted in significantly reduced tumor growth and prolonged survival. Mechanistically, these effects were mediated by two processes: cancer-cell intrinsic responses and reprogramming of the immune microenvironment that fostered a pro-inflammatory, anti-tumoral state via type I interferon signaling. These findings establish proof of concept for the therapeutic potential of targeting ADAR1 in glioblastoma, offering new strategies for the treatment of this aggressive disease. Overall design: Comparative gene expression profiling of human glioblastoma cell lines treated with 8-Azaadenosine or vehicle.