Glioblastoma-infiltrating CD8+ T cells are predominantly a clonally expanded GZMK+ effector population.

Abstract

Recent clinical trials have highlighted the limited efficacy of T cell-based immunotherapy 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 (CITE-seq) and single-cell RNA sequencing (scRNA-seq) with paired V(D)J sequencing, respectively, on TIL 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 to 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 which may harbor potential therapeutic implications.

• Authors: Anthony Z Wang, Bryce L Mashimo, Maximilian O Schaettler, Ngima D Sherpa, Lydia A Leavitt, Alexandra J Livingstone, Saad M Khan, Mao Li, Markus I Anzaldua-Campos, Joseph D Bradley, Eric C Leuthardt, Albert H Kim, Joshua L Dowling, Michael R Chicoine, Pamela S Jones, Bryan D Choi, Daniel P Cahill, Bob S Carter, Allegra A Petti, Tanner M Johanns, Gavin P Dunn
• Journal: Cancer discovery (Cancer Discov) (Feb 28 2024) ISSN: 2159-8290 [Electronic] United States
• PMID: 38416133 (Publication Type: Journal Article)