Current strategies and novel immunotherapeutic approaches for overcoming immune resistance in glioblastoma

Glioblastoma (GBM) is the most aggressive primary malignant brain tumor, characterized by rapid proliferation, extensive invasion, and significant genetic heterogeneity. Despite the availability of standard treatments such as surgical resection, radiotherapy, and chemotherapy, the prognosis for GBM patients remains poor, with a median survival of approximately 15 months. Recent advances in immunotherapy have introduced innovative approaches aimed at leveraging the immune system to specifically target and eliminate GBM cells. These strategies include cytokine-based therapies, immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell and natural killer (NK) cell therapies, RNA-based immunotherapies, and nanoparticle-mediated drug delivery systems. Furthermore, emerging technologies such as CRISPR/Cas9 gene editing, exosome-based delivery, STING pathway activation, and AI-guided personalized treatment have shown promise in overcoming the immunosuppressive tumor microenvironment and enhancing therapeutic efficacy. This review provides a comprehensive overview of these cutting-edge approaches, discussing their mechanisms, clinical potential, current limitations, and future directions for the development of more effective immunotherapies for GBM.