An immunosuppressed microenvironment distinguishes lateral ventricle-contacting glioblastomas.
Bioinformatics
Brain cancer
Immunology
Oncology
T cells
Journal
JCI insight
ISSN: 2379-3708
Titre abrégé: JCI Insight
Pays: United States
ID NLM: 101676073
Informations de publication
Date de publication:
22 06 2023
22 06 2023
Historique:
received:
05
04
2022
accepted:
08
05
2023
medline:
23
6
2023
pubmed:
16
5
2023
entrez:
16
5
2023
Statut:
epublish
Résumé
Radiographic contact of glioblastoma (GBM) tumors with the lateral ventricle and adjacent stem cell niche correlates with poor patient prognosis, but the cellular basis of this difference is unclear. Here, we reveal and functionally characterize distinct immune microenvironments that predominate in subtypes of GBM distinguished by proximity to the lateral ventricle. Mass cytometry analysis of isocitrate dehydrogenase wild-type human tumors identified elevated T cell checkpoint receptor expression and greater abundance of a specific CD32+CD44+HLA-DRhi macrophage population in ventricle-contacting GBM. Multiple computational analysis approaches, phospho-specific cytometry, and focal resection of GBMs validated and extended these findings. Phospho-flow quantified cytokine-induced immune cell signaling in ventricle-contacting GBM, revealing differential signaling between GBM subtypes. Subregion analysis within a given tumor supported initial findings and revealed intratumor compartmentalization of T cell memory and exhaustion phenotypes within GBM subtypes. Collectively, these results characterize immunotherapeutically targetable features of macrophages and suppressed lymphocytes in GBMs defined by MRI-detectable lateral ventricle contact.
Identifiants
pubmed: 37192001
pii: 160652
doi: 10.1172/jci.insight.160652
pmc: PMC10371245
doi:
pii:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NINDS NIH HHS
ID : R01 NS118580
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI125056
Pays : United States
Organisme : NCI NIH HHS
ID : F99 CA212447
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS096238
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA226833
Pays : United States
Organisme : NIH HHS
ID : S10 OD023475
Pays : United States
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