Journal article
CD155 regulates tumor growth and susceptibility to T cell mediated killing in diffuse midline glioma
Neuro-oncology (Charlottesville, Va.), Forthcoming
10 Aug 2026
PMID: 42573567
Featured in Collection : Drexel's Newest Publications
Abstract
Diffuse midline glioma (DMG) is a devastating pediatric brain tumor with an unmet need for novel therapies. Immune checkpoint inhibitors have failed to prolong survival of DMG patients.
In this study, we screened for immune checkpoint molecules in DMG, evaluated immunological responses to checkpoint targeting by co-culture assays and depletion of immune cells in vivo, studied the effects of CD155 silencing by whole-transcriptome analyses and performed in vivo treatments with Thiostrepton.
In human and murine DMG cells, as well as primary brain tumor samples, we identified CD155 as the most highly expressed immune checkpoint. When murine DMG cells were co-cultured with CD8+ T cells, silencing of CD155 led to a marked increase in T cell-mediated killing. Strikingly, CD155-deficient DMG cells failed to grow in immunocompetent mice, and depletion of CD8+ T cells allowed these tumors to grow. CD155 also exerted cell-autonomous effects on tumor cells: silencing of CD155 led to induction of apoptosis of DMG cells and delayed tumor growth in immunodeficient mice. Transcriptomic analyses identified FOXM1 as a key target of CD155. Notably, FOXM1 silencing also led to reduced proliferation of DMG cells in vitro and in vivo. Finally, treatment of DMG-bearing mice with Thiostrepton, a FOXM1-targeting agent, delayed tumor growth and prolonged survival.
These studies demonstrate that CD155 regulates immune evasion and tumor growth in DMG, and suggest that targeting CD155 could be a valuable two-pronged therapeutic strategy for this disease.
Metrics
1 Record Views
Details
- Title
- CD155 regulates tumor growth and susceptibility to T cell mediated killing in diffuse midline glioma
- Creators
- Theophilos Tzaridis - Discovery InstituteEster Calvo Fernández - Broad InstituteTanja Eisemann - Discovery InstituteAngela Liou - Discovery InstituteAugusto Faria Andrade - McGill University Health CentreCarlos A O de Biagi-Junior - Dana-Farber/Boston Children's Cancer and Blood Disorders CenterJennifer L Hope - Drexel UniversityLiam S Hewson - Hospital for Sick ChildrenMichael McNicholas - University of CambridgeAntonella De Cola - University of CambridgeManav Pathania - University of CambridgeOren J Becher - Mount Sinai HospitalNada Jabado - McGill University Health CentreJon D Larson - St. Jude Children's Research HospitalSuzanne J Baker - St. Jude Children's Research HospitalAndrea Califano - Columbia University Irving Medical CenterAnindya Bagchi - Discovery InstituteMatthew Gallitto - Columbia University Irving Medical CenterCynthia Hawkins - Hospital for Sick ChildrenMariella G Filbin - Dana-Farber/Boston Children's Cancer and Blood Disorders CenterLinda M Bradley - Discovery InstitutePeter D Adams - Discovery InstituteJovana Pavisic - Memorial Sloan Kettering Cancer CenterRobert J Wechsler-Reya (Corresponding Author) - Discovery Institute
- Publication Details
- Neuro-oncology (Charlottesville, Va.), Forthcoming
- Publisher
- Oxford University Press
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Other Identifier
- 991022201299004721