Medical Hypotheses, vol.196, 2025 (SCI-Expanded)
Glioblastoma multiforme (GBM) is the most common primary brain tumor with a 5-year median survival below 5%, despite the presence of multiple treatment modalities, including surgery, chemotherapy, radiotherapy, and immunotherapy. Tumor cells employ multiple mechanisms for evading immune system and GBM tumor microenvironment with immunosuppressive properties, and the use of immunotherapy is limited. Higher radiotherapy doses on target volumes increases neo-antigen formation, and blood brain barrier permeability. In this article, we hypothesized that lower radiation doses received by immune system tissues interacting with GBM, including cervical lymph nodes, lymphatic vessels, and bone marrow, may prevent the loss of immune system cells and disruption of immune system functions. A careful planed radiotherapy by considering immune system as an “organ at risk” may increase the immunotherapy efficiency, and overall survival in GBM patients.