Immune Landscape of Isocitrate Dehydrogenase-Stratified Primary and Recurrent Human Gliomas

Authors

Pravesh Gupta
Minghao Dang
Shivangi Oberai
Simona Migliozzi
Rakesh Trivedi
Gayatri Kumar
Mekenzie Peshoff
Nancy Milam
Aml Ahmed
Krishna Bojja
Tuan M Tran
Joy Gumin
Carlos Kamiya-Matsuoka
Jason Huse
Kathryn Cox
Jianzhuo Li
Huma Shehwana
Sameer A Sheth
Rodriguez Saxon
Sun Baohua
Brittany Parker Kerrigan
Atul Maheshwari
Edwin Roger Parra Cuentas
Nicholas E Navin
Amy B Heimberger
Frederick F Lang
Antonio Iavarone
Karen Clise-Dwyer
Linghua Wang
Krishna P Bhat

Publication Date

12-5-2024

Journal

Neuro-Oncology

DOI

10.1093/neuonc/noae139

PMID

39126294

PMCID

PMC11630528

PubMedCentral® Posted Date

8-10-2024

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Humans, Glioma, Isocitrate Dehydrogenase, Brain Neoplasms, Neoplasm Recurrence, Local, Tumor Microenvironment, Prognosis, Biomarkers, Tumor, Microglia, Single-Cell Analysis, Lymphocytes, Tumor-Infiltrating, Mutation, Transcriptome, CD8-Positive T-Lymphocytes, glioma, isocitrate dehydrogenase, microglia, tumor immune microenvironment

Published Open-Access

yes

Recommended Citation

Gupta, Pravesh; Dang, Minghao; Oberai, Shivangi; et al., "Immune Landscape of Isocitrate Dehydrogenase-Stratified Primary and Recurrent Human Gliomas" (2024). Faculty, Staff and Student Publications. 4521.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4521