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
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.
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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
- Number of pages
- 17
- Grant note
- German Research Foundation: 454298163 ChadTough Defeat DIPG Foundation National Institute on Aging: P01 AG073084 National Institute for Neurological Disorders and Stroke: R35 NS122339
This work was supported by funding from the German Research Foundation (DFG) to T.T. (Reference number: TZ 102/1-1; project number: 454298163), the ChadTough Defeat DIPG Foundation to T.T., the National Institute for Neurological Disorders and Stroke (R35 NS122339 to R.J.W.-R.) and the National Institute on Aging (P01 AG073084 to P.D.A.). Additional support was provided by the Swim Across America and Team Jack Foundations to J.P. SBP's Shared Resources are supported by SBP's NCI Cancer Center Support Grant P30 CA030199. R.J.W.-R.'s laboratory was also funded by the Ian's Friends Foundation, Alex's Lemonade Stand Foundation, the V Foundation, William's Superhero Fund, and the McDowell Charity Trust. This work was supported by the NCI Office of Cancer Target Discovery and Development (CTD2) award U01CA272610, and the NCI Outstanding Investigator award R35CA197745, all to A.C. Further support was provided through the Postgraduate studies in North America and the Asia-Pacific region Fellowship by "La Caixa Foundation" and the Trainee Associate Member (TAM) predoctoral award from the Herbert Irving Comprehensive Cancer and Education Coordination centers at Columbia University, both awarded to E.C.F.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:001865523300001
- Other Identifier
- 991022201299004721