Tumor infiltrating lymphocytes in glioblastoma: immunobiology and translational implications

Glioblastoma (GBM) poses unique challenges to immunotherapy, owing to its low tumor mutational burden, profound antigenic heterogeneity, and highly immunosuppressive microenvironment. Observations of tumor-infiltrating lymphocytes (TILs) in human GBM differ from those in syngeneic orthotopic murine models: whereas TILs in several widely used murine glioma models display an abundance of exhausted T cells, patient tumors are enriched for clonally expanded granzyme K⁺ T cells of uncertain function. We review the current understanding of the brain tumor immunity cycle in GBM, highlight the translational implications of TIL biology, and evaluate emerging TCR-based approaches, including adoptive TILs transfer, neoantigen vaccines, and engineered receptors. A refined focus on identifying and harnessing tumor-selective T cells may enable more rational, personalized immunotherapies for GBM.