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Characterization of distinct immunophenotypes across pediatric brain tumor types.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Griesinger, Andrea M. Wang, Michael Amani, Vladimir Handler, Michael H. Donson, Andrew M. Foreman, Nicholas K. Hoffman, Lindsey M. Waziri, Allen Birks, Diane K.
Description	Author Affiliation: Griesinger AM ( Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045)
Abstract	Despite increasing evidence that antitumor immune control exists in the pediatric brain, these findings have yet to be exploited successfully in the clinic. A barrier to development of immunotherapeutic strategies in pediatric brain tumors is that the immunophenotype of these tumors' microenvironment has not been defined. To address this, the current study used multicolor FACS of disaggregated tumor to systematically characterize the frequency and phenotype of infiltrating immune cells in the most common pediatric brain tumor types. The initial study cohort consisted of 7 pilocytic astrocytoma (PA), 19 ependymoma (EPN), 5 glioblastoma (GBM), 6 medulloblastoma (MED), and 5 nontumor brain (NT) control samples obtained from epilepsy surgery. Immune cell types analyzed included both myeloid and T cell lineages and respective markers of activated or suppressed functional phenotypes. Immune parameters that distinguished each of the tumor types were identified. PA and EPN demonstrated significantly higher infiltrating myeloid and lymphoid cells compared with GBM, MED, or NT. Additionally, PA and EPN conveyed a comparatively activated/classically activated myeloid cell-skewed functional phenotype denoted in particular by HLA-DR and CD64 expression. In contrast, GBM and MED contained progressively fewer infiltrating leukocytes and more muted functional phenotypes similar to that of NT. These findings were recapitulated using whole tumor expression of corresponding immune marker genes in a large gene expression microarray cohort of pediatric brain tumors. The results of this cross-tumor comparative analysis demonstrate that different pediatric brain tumor types exhibit distinct immunophenotypes, implying that specific immunotherapeutic approaches may be most effective for each tumor type.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1301966
Journal	The Journal of Immunology
Issue Number	9
Volume Number	191
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2013-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Brain Neoplasms Classification Immunology Immunophenotyping Myeloid Cells T-lymphocytes Adolescent Astrocytoma Brain Genetics Cohort Studies Ependymoma Epilepsy Gene Expression Profiling Gene Expression Regulation, Neoplastic Glioblastoma Hla-dr Antigens Metabolism Medulloblastoma Receptors, Igg Tumor Microenvironment Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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