Abstract
Background. Human gliomas are classified using isocitrate dehydrogenase (IDH) status as a prognosticator; however, the influence of genetic differences and treatment effects on ensuing immunity remains unclear. Methods. In this study, we used sequential single-cell transcriptomics on 144 678 and spectral cytometry on over 2 million immune cells encompassing 48 human gliomas to decipher their immune landscape. Results. We identified 22 distinct immune cell types that contribute to glioma immunity. Specifically, brain-resident microglia (MG) were reduced with a concomitant increase in CD8+ T lymphocytes during glioma recurrence independent of IDH status. In contrast, IDH-wild type-associated patterns, such as an abundance of antigen-presenting cell-like MG and cytotoxic CD8+ T cells, were observed. Beyond elucidating the differences in IDH, relapse, and treatment-associated immunity, we discovered novel inflammatory MG subpopulations expressing granulysin, a cytotoxic peptide that is otherwise expressed in lymphocytes only. Furthermore, we provide a robust genomic framework for defining macrophage polarization beyond M1/M2 paradigm and reference signatures of glioma-specific tumor immune microenvironment (termed GlioTIME-36) for deconvoluting transcriptomic datasets. Conclusions. This study provides advanced optics of the human pan-glioma immune contexture as a valuable guide for translational and clinical applications.
Original language | English (US) |
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Pages (from-to) | 2239-2255 |
Number of pages | 17 |
Journal | Neuro-oncology |
Volume | 26 |
Issue number | 12 |
DOIs | |
State | Published - Dec 1 2024 |
Keywords
- glioma
- isocitrate dehydrogenase
- microglia
- tumor immune microenvironment
ASJC Scopus subject areas
- Oncology
- Clinical Neurology
- Cancer Research