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