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J Neurooncol. 2018 Apr;137(2):269-278. doi: 10.1007/s11060-017-2737-9. Epub 2018 Jan 10.

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

Author information

1
Pediatric Neuro-Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA. ashley.s.plant@gmail.com.
2
Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
3
Pediatric Hematology/Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA.
4
Department of Pathology, Brigham and Women's Hospital, Amory 3, 75 Francis Street, Boston, MA, 02115, USA.
5
Division of Neuro-Pathology, Department of Pathology, Brigham and Women's Hospital, 75 Francis St, Boston, MA, 02115, USA.
6
Pediatric Neuro-Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA.
7
Harvard T.H. Chan School of Public Health, 655 Huntington Ave, Building II Room 421, Boston, MA, 02115, USA.
8
Adpative Technologies Corp, 1551 Eastlake Ave E Ste 200, Seattle, WA, 98102, USA.
9
Novartis Institutes for Biomedical Research, 250 Massachusetts Ave, Cambridge, MA, 02139, USA.
10
Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA.

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.

KEYWORDS:

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

PMID:
29322427
DOI:
10.1007/s11060-017-2737-9
[Indexed for MEDLINE]

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