Glioblastoma-Infiltrating CD8⁺ T Cells Are Predominantly a Clonally Expanded GZMK⁺ Effector Population

Recent clinical trials have highlighted the limited efficacy of T cell–based immuno-therapy in patients with glioblastoma (GBM). To better understand the characteristics of tumor-infiltrating lymphocytes (TIL) in GBM, we performed cellular indexing of transcriptomes and epitopes by sequencing and single-cell RNA sequencing with paired V(D)J sequencing, respectively, on TILs from two cohorts of patients totaling 15 patients with high-grade glioma, including GBM or astrocytoma, IDH-mutant, grade 4 (G4A). Analysis of the CD8⁺ TIL landscape reveals an enrichment of clonally expanded GZMK⁺ effector T cells in the tumor compared with matched blood, which was validated at the protein level. Furthermore, integration with other cancer types highlights the lack of a canonically exhausted CD8⁺ T-cell population in GBM TIL. These data suggest that GZMK⁺ effector T cells represent an important T-cell subset within the GBM microenvironment and may harbor potential therapeutic implications.