Recent developments in nanotechnology-enhanced immunotherapy for glioblastoma.

Abstract

Glioblastoma (GBM) is the most aggressive form of primary brain tumor and remains associated with dismal clinical outcomes despite the use of multimodal treatment strategies. In recent years, immunotherapy has gained increasing attention as a novel paradigm in cancer treatment. Unlike conventional therapies that directly target tumor cells, immunotherapy seeks to harness the host immune system to eradicate malignancies. However, the profoundly immunosuppressive tumor microenvironment characteristic of GBM severely limits the effectiveness of immunotherapeutic approaches. In addition, the blood-brain barrier (BBB) poses a formidable obstacle to the delivery of therapeutic agents to intracranial tumors. Consequently, effective immunotherapy for GBM requires strategies that both enable efficient BBB penetration and overcome local immunosuppression within the tumor microenvironment. This review first summarizes the immune system of the central nervous system (CNS), the immunosuppressive mechanisms underlying GBM progression, and current immunotherapeutic strategies for GBM. We then discuss recent advances in nanomaterial-based immunotherapy for GBM, focusing on four major approaches: immune checkpoint inhibition, targeting tumor-associated immune cells, stimulation of immune responses via immunogenic cell death, and combination therapies. This narrative review was conducted through a literature search of major biomedical databases, focusing on studies related to GBM immunotherapy and nanomaterial-based therapeutic strategies.