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Therapeutic implications of CD1d expression and tumor-infiltrating macrophages in pediatric medulloblastomas

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ABSTRACT

Immunobiology of medulloblastoma (MB), the most common malignant brain tumor in children, is poorly understood. Although tumor cells in some MBs were recently shown to express CD1d and be susceptible to Vα24-invariant natural killer T (NKT)-cell cytotoxicity, the clinical relevance of CD1d expression in MB patients remains unknown. We investigated the expression of CD1d in pediatric MBs and correlated with molecular and clinical characteristics. Specifically, we explored if NKT cell therapy can be targeted at a subset of pediatric MBs with poorer prognosis. Particularly, infantile MBs have a worse outcome because radiotherapy is delayed to avoid neurocognitive sequelae. Immunohistochemistry for CD1d was performed on a screening set of 38 primary pediatric MBs. Gene expression of the membrane form of M2 macrophage marker, CD163, was studied in an expanded cohort of 60 tumors. Outcome data was collected prospectively. Thirteen of 38 MBs (34.2 %) expressed CD1d on immunohistochemistry. CD1d was expressed mainly on MB tumor cells, and on some tumor-associated macrophages. Majority (18/22, 82 %) of non sonic-hedgehog/Wingless-activated MBs (group 3 and 4) were CD1d-negative (p = 0.05). A subset of infantile MBs (4/9, 44.4 %) expressed CD1d. Macrophages infiltrating MB expressed CD163 apart from CD1d. Molecular subtypes demonstrated statistical differences in CD163 expression, SHH-tumors were the most enriched (p = 0.006). Molecular and clinical subtypes of pediatric MB exhibit distinct differences in CD1d expression, which have important therapeutic implications. High CD1d expression in infantile MBs offers potential new immunotherapeutic treatment with NKT cell therapy in infants, where treatment is suboptimal due delayed radiotherapy.

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Acknowledgments

Supported by NIH Grant CA109467 and Grants from the Gillson Longenbaugh Foundation, John S. Dunn Research Foundation, the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation and National Medical Research Council Research Fellowship (Singapore).

Conflict of interests

All the authors declared no competing or conflict of interests, or financial disclosures that are relevant to the subject matter under consideration in this article.

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Author notes

  1. Wan-Yee Teo

    Present address: Department of Pediatrics, Inova Children’s Hospital, Inova Fairfax Medical Campus, 3300 Gallows Road, Falls Church, VA, 22042, USA

Authors and Affiliations

  1. Department of Pediatrics, Division of Hematology-Oncology, Texas Children’s Cancer and Hematology Centers, 1102 Bates street, 1030.11, Feigin Center, Houston, TX, 77030, USA

    Wan-Yee Teo, Jianhe Shen, Tsz-Kwong Man, Xiaonan Li, Murali Chintagumpala, Jack Meng Fen Su & Ching C. Lau

  2. Department of Pathology, Baylor College of Medicine, Houston, TX, USA

    Adekunle M. Adesina

  3. Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA

    Tsz-Kwong Man, Xiaonan Li, Murali Chintagumpala, Jack Meng Fen Su, Robert Dauser, William Whitehead, Adekunle M. Adesina & Ching C. Lau

  4. Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA

    Robert Dauser & William Whitehead

  5. Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA

    M. Tarek Elghetany

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Correspondence to Wan-Yee Teo or Ching C. Lau.

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Wan-Yee Teo and Ching C. Lau are Co-Corresponding authors.

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Teo, WY., Elghetany, M.T., Shen, J. et al. Therapeutic implications of CD1d expression and tumor-infiltrating macrophages in pediatric medulloblastomas. J Neurooncol 120, 293–301 (2014). https://doi.org/10.1007/s11060-014-1572-5

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  • DOI: https://doi.org/10.1007/s11060-014-1572-5

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