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CD155 is a putative therapeutic target in medulloblastoma

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Abstract

Background

Medulloblastoma is the most common pediatric malignant brain tumor, consisting of four molecular subgroups (WNT, SHH, Group 3, Group 4) and 12 subtypes. Expression of the cell surface poliovirus receptor (PVR), CD155, is necessary for entry of the viral immunotherapeutic agent, PVSRIPO, a polio:rhinovirus chimera. CD155, physiologically expressed in the mononuclear phagocytic system, is widely expressed ectopically in solid tumors. The objective of this study is to elucidate CD155 expression as both a receptor for PVSRIPO and a therapeutic target in medulloblastoma.

Methods

PVR mRNA expression was determined in several patient cohorts and human medulloblastoma cell lines. Patient samples were also analyzed for CD155 expression using immunohistochemistry and cell lines were analyzed using Western Blots. CD155 was blocked using a monoclonal antibody and cell viability, invasion, and migration were assessed.

Results and Discussion

PVR mRNA expression was highest in the WNT subgroup and lowest in Group 4. PVR expression in the subgroups of medulloblastoma were similar to other pediatric brain and non-brain tumors. PVR expression was largely not associated with subgroup or subtype. Neither PVR protein expression intensity nor frequency were associated with overall survival. PVR expression was elevated in Group 3 patients with metastases but there was no difference in paired primary and metastatic medulloblastoma. Blocking PVR resulted in dose-dependent cell death, decreased invasion in vitro, and modestly inhibited cell migration.

Conclusions

CD155 is expressed across medulloblastoma subgroups and subtypes. Blocking CD155 results in cell death and decreased cellular invasion. This study provides rationale for CD155-targeting agents including PVSRIPO and antibody-mediated blockade of CD155.

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Acknowledgements

The authors wish to thank lab members for technical support, Beth Perry for IRB assistance, Samuel Dell for technical assistance, and the Preston Robert Tisch Brain Tumor Center personnel for assistance with human specimens.

Funding

EMT: Department of Defense CA171067, Musella Foundation for Brain Tumor Research & Information, Chetna & Meena Trust. The Preston Robert Tisch Brain Tumor Center Biorespository is supported by the Pediatric Brain Tumor Foundation.

Author information

Authors and Affiliations

  1. Duke University, Durham, NC, USA

    Sean Li

  2. Department of Pathology, Duke University, Durham, NC, USA

    Roger McLendon & Eric Michael Thompson

  3. Department of Neurosurgery, Duke University Medical Center, Box 3272, Durham, NC, 27710, USA

    Eric Sankey, Reb Kornahrens, Zachary McKay, Matthias Gromeier, Michael Brown & Eric Michael Thompson

  4. Institut Curie, PSL Research University, 75005, Paris, France

    Anne-Marie Lyne & Florence Marie Géraldine Cavalli

  5. Inserm, U900, Paris, France

    Anne-Marie Lyne & Florence Marie Géraldine Cavalli

  6. MINES ParisTech, CBIO, Centre for Computational Biology, PSL Research University, 75006, Paris, France

    Anne-Marie Lyne & Florence Marie Géraldine Cavalli

  7. Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA

    James Emmett Herndon II

  8. Department of Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany

    Marc Remke & Daniel Picard

  9. Department of Pediatric Neuro-Oncogenomics, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany

    Daniel Picard

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  1. Sean Li
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Contributions

EMT designed research; SL, RM ES, RK, AML, FMGC, MB, and EMT performed research; all authors analyzed and interpreted data, SL and EMT wrote the manuscript. All authors reviewed/revised the manuscript.

Corresponding author

Correspondence to Eric Michael Thompson.

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Conflict of interest

MG and MB own intellectual property related to PVSRIPO, which has been licensed to Istari Oncology, Inc. MG holds equity in Istari Oncology, Inc.; MG and MB received consultancy fees from Istari Oncology, Inc.

Ethical approval

Patient studies were approved by the Duke University Institutional Review Board (Pro00085537).

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Informed consent was not required from patients or their families as all specimens were obtained retrospectively and were de-identified.

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Li, S., McLendon, R., Sankey, E. et al. CD155 is a putative therapeutic target in medulloblastoma. Clin Transl Oncol 25, 696–705 (2023). https://doi.org/10.1007/s12094-022-02975-9

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