Journal Article

DKFZ-2026-00195

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png IGSF11-VISTA is a critical and targetable immune checkpoint axis in diffuse midline glioma.

Collot, R. ; Ruiz-Moreno, C. ; Honhoff, C. ; van den Broek, T. J. M. ; Wezenaar, A. K. L. ; Kloosterman, D. J. ; Ariese, H. C. R. ; Johnson, H. ; Vervoort, B. M. T. ; Jeiroshi, A. ; Bunt, J. ; van Ineveld, R. L. ; Bokobza, E. ; Rebel, H. G. ; Te Pas, B. M. ; Ringnalda, F. C. A. ; van de Wetering, M. ; Robe, P. A. ; Kool, M.DKFZ* ; Cochran, J. R. ; Kranendonk, M. E. G. ; van Vuurden, D. G. ; Hulleman, E. ; Wehrens, E. J. ; Zomer, A. ; Stunnenberg, H. G. ; Rios, A. C.

2026
Cell Press Cambridge, Mass.

Abstract: 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.

Keyword(s): IGSF11-VISTA immune checkpoint ; cancer-immune landscape ; diffuse midline glioma ; microglia-cancer interaction ; spatial multi-omics profiling

Note: epub

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Contributing Institute(s):

1. B062 Pädiatrische Neuroonkologie (B062)
2. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2026

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 50 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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