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Supplementary_Fig_S10 from Glioblastoma-Infiltrating CD8+ T Cells Are Predominantly a Clonally Expanded GZMK+ Effector Population

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posted on 2024-06-03, 07:41 authored by 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

Comparison of TIL from primary and recurrent GBM samples.

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Cancer Research Institute (CRI)

National Cancer Institute (NCI)

United States Department of Health and Human Services

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Cancer Research Foundation (CRF)

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ARTICLE 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 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. To understand the limited efficacy of immune-checkpoint blockade in GBM, we applied a multiomics approach to understand the TIL landscape. By highlighting the enrichment of GZMK+ effector T cells and the lack of exhausted T cells, we provide a new potential mechanism of resistance to immunotherapy in GBM.This article is featured in Selected Articles from This Issue, p. 897

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