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

Ashley S. Plant, Shohei Koyama, Claire Sinai, Isaac H. Solomon, Gabriel K. Griffin, Keith L. Ligon, Pratiti Bandopadhayay, Rebecca Betensky, Ryan Emerson, Glenn Dranoff, Mark W. Kieran, Jerome Ritz

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)269-278
Number of pages10
JournalJournal of Neuro-Oncology
Volume137
Issue number2
DOIs
StatePublished - Apr 1 2018

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Immunophenotyping
Brain Neoplasms
Histology
Pediatrics
T-Lymphocytes
Survival
Neoplasms
Immunohistochemistry
Glioma
Flow Cytometry
Biomarkers
Regulatory T-Lymphocytes
Immunosuppressive Agents
T-Cell Antigen Receptor
Immune System
Phenotype
Research

Keywords

  • Flow cytometry
  • Immune infiltrate
  • Immunohistochemistry
  • Immunotherapy
  • Mutational load
  • Pediatric brain tumors
  • T cell receptor

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

Immunophenotyping of pediatric brain tumors : correlating immune infiltrate with histology, mutational load, and survival and assessing clonal T cell response. / Plant, Ashley S.; Koyama, Shohei; Sinai, Claire; Solomon, Isaac H.; Griffin, Gabriel K.; Ligon, Keith L.; Bandopadhayay, Pratiti; Betensky, Rebecca; Emerson, Ryan; Dranoff, Glenn; Kieran, Mark W.; Ritz, Jerome.

In: Journal of Neuro-Oncology, Vol. 137, No. 2, 01.04.2018, p. 269-278.

Research output: Contribution to journalArticle

Plant, AS, Koyama, S, Sinai, C, Solomon, IH, Griffin, GK, Ligon, KL, Bandopadhayay, P, Betensky, R, Emerson, R, Dranoff, G, Kieran, MW & Ritz, J 2018, 'Immunophenotyping of pediatric brain tumors: correlating immune infiltrate with histology, mutational load, and survival and assessing clonal T cell response', Journal of Neuro-Oncology, vol. 137, no. 2, pp. 269-278. https://doi.org/10.1007/s11060-017-2737-9
Plant, Ashley S. ; Koyama, Shohei ; Sinai, Claire ; Solomon, Isaac H. ; Griffin, Gabriel K. ; Ligon, Keith L. ; Bandopadhayay, Pratiti ; Betensky, Rebecca ; Emerson, Ryan ; Dranoff, Glenn ; Kieran, Mark W. ; Ritz, Jerome. / Immunophenotyping of pediatric brain tumors : correlating immune infiltrate with histology, mutational load, and survival and assessing clonal T cell response. In: Journal of Neuro-Oncology. 2018 ; Vol. 137, No. 2. pp. 269-278.
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