The Tumour Immune Microenvironment in Glioblastoma: Implications for Immunotherapy Failure and Future Directions

Abstract

Glioblastoma accounts for 14.5% of all central nervous system (CNS) tumours. Current immunotherapeutic strategies include surgery, radiotherapy, and chemotherapy, with an increased focus on checkpoint inhibitors and CAR-T cell therapy. However, these have demonstrated limited clinical effectiveness due to the tumour’s ability to generate and sustain pro-tumourigenic immune microenvironments (TIME), T-cell exhaustion, and myeloid-derived suppressor cell activity. In order to overcome these limitations, future directions emphasise multimodal approaches, including oncolytic virotherapy and nanoparticle-based delivery systems, to improve therapeutic outcomes. Keywords: Glioblastoma, high-grade glioma, tumour immune microenvironments, immunotherapy, CART cell therapy, nanoparticle-based delivery.