Immunological Biomarkers in Glioblastoma: Targeting T and NK Cells for Enhanced Diagnosis and Prognosis

Glioblastoma (GBM) is an aggressive brain tumor with a poor prognosis, even with many therapeutic interventions, including surgery, chemotherapy, and radiotherapy. Recent immunotherapies have broaden horizons to the utilization of the immune system to eradicate GBM. However, the clinical efficacy of such approaches is limited, owing to the tumor's multifaceted immunosuppressive microenvironment and the blood-brain barrier (BBB) structure. The dysfunction of immune cells, especially T cells and natural killer (NK) cells, is significantly influenced by the immunosuppressive mechanisms in GBM. Novel therapeutic strategies are needed to overcome these mechanisms. In the current review, we explore the main functions of T cells, especially cytotoxic CD4⁺ and helper CD8⁺ T cells, alongside NK cells, in response to GBM. We further discuss the mechanisms contributing to their dysfunction, focusing on T cell exhaustion, altered receptor expression, and metabolic reprogramming within the GBM microenvironment to establish diagnostic and prognostic biomarkers. Moreover, we highlight recent advances in immunotherapeutic approaches, including immune checkpoint inhibitors (ICI), miRNA therapy, oncolytic viruses, and Chimeric Antigen Receptor (CAR) T/NK cell therapy to provide new opportunities for enhancing GBM treatment and biomarker-guided precision medicine.