Work package B07A is associated to UNITE and funded with ressources outside of the Collaborative Research Center (CRC) 1389.
In this work package, we will investigate the resistance of pediatric high-grade glioma to commonly used radiotherapy. Radioresistance will be induced in a unique portfolio of immunocompetent mouse models and molecularly analyzed for tumor-intrinsic mediators and factors in the tumor microenvironment (TME). Identified players will be validated genetically and subsequently targeted in derived combinatorial trials. TME-related factors will be investigated in vivo and combined with a first-in-class inhibitor of the chemokine CXCL12. In a complementary approach, DNA Damage Response inhibitors will be used to overcome radioresistance by enhancing immunogenic cell death in vitro and in vivo.