Gemistocytic tumor cells programmed for glial scarring characterize T cell confinement in IDH-mutant astrocytoma.

Details

Ressource 1Download: 39880824_BIB_20E8DAD3C94B.pdf (3328.06 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_20E8DAD3C94B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Gemistocytic tumor cells programmed for glial scarring characterize T cell confinement in IDH-mutant astrocytoma.
Journal
Nature communications
Author(s)
van Hijfte L., Geurts M., de Heer I., Ghisai S.A., Balcioglu H.E., Hoogstrate Y., Vallentgoed W.R., Head R., Luning R., van den Bosch T., Westerman B., Wesseling P., Joyce J.A., French P., Debets R.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
29/01/2025
Peer-reviewed
Oui
Volume
16
Number
1
Pages
1156
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Isocitrate dehydrogenase 1/2 mutant (IDHmt) astrocytoma is considered a T cell-deprived tumor, yet little is known regarding the phenotypes underlying T cell exclusion. Using bulk, single nucleus and spatial RNA and protein profiling, we demonstrate that a distinct spatial organization underlies T cell confinement to the perivascular space (T cell cuff) in IDHmt astrocytoma. T cell cuffs are uniquely characterized by a high abundance of gemistocytic tumor cells (GTC) in the surrounding stroma. Integrative analysis shows that GTC-high tumors are enriched for lymphocytes and tumor associated macrophages (TAM) and express immune cell migration and activation programs. Specifically, GTCs constitute a distinct sub-cluster of the astrocyte-like tumor cell state that co-localizes with immune reactive TAMs. Neighboring GTCs and TAMs express receptor-ligand pairs characteristic of reactive astrogliosis and glial scarring, such as SPP1/CD44 and IL-1β/IL1R1. Collectively, we reveal that T cell confinement in IDHmt astrocytomas associates with GTC-TAM networks that mimic glial scarring mechanisms.
Keywords
Humans, Isocitrate Dehydrogenase/genetics, Isocitrate Dehydrogenase/metabolism, Astrocytoma/genetics, Astrocytoma/pathology, Astrocytoma/immunology, T-Lymphocytes/immunology, T-Lymphocytes/metabolism, Mutation, Brain Neoplasms/genetics, Brain Neoplasms/pathology, Brain Neoplasms/immunology, Tumor-Associated Macrophages/immunology, Tumor-Associated Macrophages/metabolism, Astrocytes/metabolism, Astrocytes/pathology, Tumor Microenvironment/immunology, Tumor Microenvironment/genetics, Gliosis/pathology, Gliosis/genetics, Cell Movement
Pubmed
Web of science
Open Access
Yes
Create date
31/01/2025 17:24
Last modification date
27/02/2025 8:07
Usage data