TNF and glioblastoma: The escalation of c-Jun N-terminal kinase (JNK) pathway signaling in GBM is attributed to the interaction between the receptor Grindelwald (Grnd) and the ligand Eiger (Egr)/TNFα, which is produced by the surrounding non-cancerous brain tissue, according to a study by Portela et al. This study suggests that interactions between GBM cells and adjacent healthy brain tissue may instigate TME expansion, and that such extrinsic signals are instrumental in advancing GBM [135].