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Immunophenotyping of pediatric brain tumors: correlating immune infiltrate with histology, mutational load, and survival and assessing clonal T cell response

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Abstract

There is little known regarding the immune infiltrate present in pediatric brain tumors and how this compares to what is known about histologically similar adult tumors and its correlation with survival. Here, we provide a descriptive analysis of the immune infiltrate of 22 fresh pediatric brain tumor tissue samples of mixed diagnoses and 40 peripheral blood samples. Samples were analyzed using a flow cytometry panel containing markers for immune cell subtypes, costimulatory markers, inhibitory signals, and markers of activation. This was compared to the standard method of immunohistochemistry (IHC) for immune markers for 89 primary pediatric brain tumors. Both flow cytometry and IHC data did not correlate with the grade of tumor or mutational load and IHC data was not significantly associated with survival for either low grade or high grade gliomas. There is a trend towards a more immunosuppressive phenotype in higher grade tumors with more regulatory T cells present in these tumor types. Both PD1 and PDL1 were present in only a small percentage of the tumor infiltrate. T cell receptor sequencing revealed up to 10% clonality of T cells in tumor infiltrates and no significant difference in clonality between low and high grade gliomas. We have shown the immune infiltrate of pediatric brain tumors does not appear to correlate with grade or survival for a small sample of patients. Further research and larger studies are needed to fully understand the interaction of pediatric brain tumors and the immune system.

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Funding

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number K12CA090354. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The portion of this project involving T cell receptor sequencing was supported by a Young Investigator Award supported by Adaptive Biotechnologies.

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Authors and Affiliations

  1. Pediatric Neuro-Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA

    Ashley S. Plant, Pratiti Bandopadhayay & Mark W. Kieran

  2. Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Shohei Koyama

  3. Pediatric Hematology/Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA

    Claire Sinai

  4. Department of Pathology, Brigham and Women’s Hospital, Amory 3, 75 Francis Street, Boston, MA, 02115, USA

    Isaac H. Solomon & Gabriel K. Griffin

  5. Division of Neuro-Pathology, Department of Pathology, Brigham and Women’s Hospital, 75 Francis St, Boston, MA, 02115, USA

    Keith L. Ligon

  6. Harvard T.H. Chan School of Public Health, 655 Huntington Ave, Building II Room 421, Boston, MA, 02115, USA

    Rebecca Betensky

  7. Adpative Technologies Corp, 1551 Eastlake Ave E Ste 200, Seattle, WA, 98102, USA

    Ryan Emerson

  8. Novartis Institutes for Biomedical Research, 250 Massachusetts Ave, Cambridge, MA, 02139, USA

    Glenn Dranoff

  9. Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA

    Jerome Ritz

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  1. Ashley S. Plant
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Correspondence to Ashley S. Plant.

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Conflict of interest

Ashley Plant has no conflict of interest to disclose except that she is the recipient of the Young Investigator Award from Biotechnologies Incorporated in the amount of $5000 to support this project. Shohei Koyama has no conflict of interest to disclose. Claire Sinai has no conflict of interest to disclose. Isaac Solomon has no conflict of interest to disclose. Gabriel Griffin has no conflict of interest to disclose relevant to this project but does participate in consulting activities for Moderna Therapeutics. Keith Ligon has no conflict of interest to disclose related to the project. Pratiti Bandopadhayay has no conflict of interest to disclose. Rebecca Betensky has no conflict of interest to disclose. Ryan Emerson is an employee of Adaptive Biotechnologies Incorporated but, otherwise, has no conflict of interest to disclose. Glenn Dranoff became an employee of Novartis Institutes of Biomedical Research during the formation of this project but otherwise has no other conflict of interest to disclose. Mark W. Kieran has no conflict of interest to disclose related to this project. Jerome Ritz has no conflict of interest to disclose related to this project.

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No animals were used in this study. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study prior to any tissue or blood sample collection.

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Plant, A.S., Koyama, S., Sinai, C. et al. Immunophenotyping of pediatric brain tumors: correlating immune infiltrate with histology, mutational load, and survival and assessing clonal T cell response. J Neurooncol 137, 269–278 (2018). https://doi.org/10.1007/s11060-017-2737-9

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  • DOI: https://doi.org/10.1007/s11060-017-2737-9

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