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This review aims to explore the roles of T and NK cells in glioblastoma, focusing on their dysfunction and potential as biomarkers.

May 31, 2026Biologics0 citationsOpen Access

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

AAAmir Mohammad Akbari SBShahriyar Bourbour MSMaryam Sadat Seyedmehdi

Key Points

This review aims to explore the roles of T and NK cells in glioblastoma, focusing on their dysfunction and potential as biomarkers.
Review of current therapeutic strategies targeting T and NK cells in GBM.
Discussion of T cell exhaustion, receptor alterations, and metabolic reprogramming in the tumor microenvironment.
Evaluation of novel immunotherapeutic approaches such as CAR T/NK cell therapy and immune checkpoint inhibitors.
Dysfunction of T and NK cells in GBM is closely linked to the immunosuppressive microenvironment and BBB.
Emerging therapies like immune checkpoint inhibitors and CAR therapy show promise in overcoming GBM challenges.
Established diagnostic and prognostic biomarkers may improve patient outcomes and treatment precision.

Abstract

Abstract: 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. Keywords: glioblastoma, tumor microenvironment, immunotherapy, oncolytic viruses, immune checkpoint inhibitors, miRNA Therapy

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