TY  - JOUR
AU  - Collot, Raphaël
AU  - Ruiz-Moreno, Cristian
AU  - Honhoff, Celina
AU  - van den Broek, Thijs J M
AU  - Wezenaar, Amber K L
AU  - Kloosterman, Daan J
AU  - Ariese, Hendrikus C R
AU  - Johnson, Hannah
AU  - Vervoort, Britt M T
AU  - Jeiroshi, Amal
AU  - Bunt, Jens
AU  - van Ineveld, Ravian L
AU  - Bokobza, Emma
AU  - Rebel, Heggert G
AU  - Te Pas, Brigit M
AU  - Ringnalda, Femke C A
AU  - van de Wetering, Marc
AU  - Robe, Pierre A
AU  - Kool, Marcel
AU  - Cochran, Jennifer R
AU  - Kranendonk, Mariëtte E G
AU  - van Vuurden, Dannis G
AU  - Hulleman, Esther
AU  - Wehrens, Ellen J
AU  - Zomer, Anoek
AU  - Stunnenberg, Hendrik G
AU  - Rios, Anne C
TI  - IGSF11-VISTA is a critical and targetable immune checkpoint axis in diffuse midline glioma.
JO  - Cancer cell
VL  - nn
SN  - 1535-6108
CY  - Cambridge, Mass.
PB  - Cell Press
M1  - DKFZ-2026-00195
SP  - nn
PY  - 2026
N1  - epub
AB  - Diffuse midline glioma (DMG) is an aggressive pediatric brain tumor with no curative treatment, and lacks a comprehensive understanding of immune-tumor cell interactions within their spatial context. Our multi-omics approach, integrating single-nuclei RNA sequencing, spatial transcriptomics, and high-dimensional imaging, utilizes patient samples and an experimental murine DMG model to unveil two spatially distinct regions. MES-patterns are defined by mesenchymal (MES) tumor cells and blood-derived immune cells, whereas AOO-patterns are enriched with astrocyte (AC)-, oligodendrocyte (OC)-, and oligodendrocyte precursor cell (OPC)-like cancer populations, alongside homeostatic-like microglia. The less-studied immune checkpoint, IGSF11, is primarily expressed by AOO-associated cancer cells, while its receptor VISTA is detected mainly in homeostatic microglia. Targeting IGSF11-VISTA results in tumor reduction and survival benefit, mediated by brain-resident microglia and independent of T cell infiltration. This positions IGSF11-VISTA as a promising immune checkpoint treatment axis to harness the local brain immune response against DMG.
KW  - IGSF11-VISTA immune checkpoint (Other)
KW  - cancer-immune landscape (Other)
KW  - diffuse midline glioma (Other)
KW  - microglia-cancer interaction (Other)
KW  - spatial multi-omics profiling (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41576930
DO  - DOI:10.1016/j.ccell.2025.12.020
UR  - https://inrepo02.dkfz.de/record/308662
ER  -