Immune Gene and Cell Enrichment Is Associated with a Good Prognosis in Ependymoma

被引:47
作者
Donson, Andrew M. [1 ,4 ]
Birks, Diane K. [3 ,4 ]
Barton, Valerie N. [1 ,4 ]
Wei, Qi [1 ,4 ]
Kleinschmidt-DeMasters, Bette K. [2 ]
Handler, Michael H. [3 ,4 ]
Waziri, Allen E. [3 ]
Wang, Michael [1 ,4 ]
Foreman, Nicholas K. [1 ,3 ,4 ]
机构
[1] Univ Colorado Denver, Dept Pediat, Aurora, CO 80045 USA
[2] Univ Colorado Denver, Dept Pathol & Neurol, Aurora, CO 80045 USA
[3] Univ Colorado Denver, Dept Neurosurg, Aurora, CO 80045 USA
[4] Childrens Hosp, Denver, CO 80045 USA
关键词
CHOROID-PLEXUS TUMORS; INTRACRANIAL EPENDYMOMAS; EXPRESSION; MICROGLIA; CHILDREN; SURVIVAL; ACTIVATION; CHILDHOOD; IDENTIFICATION; PROLIFERATION;
D O I
10.4049/jimmunol.0902811
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Approximately 50% of children with ependymoma will suffer from tumor recurrences that will ultimately lead to death. Development of more effective therapies and patient stratification in ependymoma mandates better prognostication. In this study, tumor gene expression microarray profiles from pediatric ependymoma clinical samples were subject to ontological analyses to identify outcome-associated biological factors. Histology was subsequently used to evaluate the results of ontological analyses. Ontology analyses revealed that genes associated with nonrecurrent ependymoma were predominantly immune function-related. Additionally, increased expression of immune-related genes was correlated with longer time to progression in recurrent ependymoma. Of those genes associated with both the nonrecurrent phenotype and that positively correlated with time to progression, 95% were associated with immune function. Histological analysis of a subset of these immune function genes revealed that their expression was restricted to a subpopulation of tumor-infiltrating cells. Analysis of tumor-infiltrating immune cells showed increased infiltration of CD4(+) T cells in the nonrecurrent ependymomas. No genomic sequences for SV40, BK, JC, or Merkel polyomaviruses were found in nonrecurrent ependymoma. This study reveals that up-regulation of immune function genes is the predominant ontology associated with a good prognosis in ependymoma and it provides preliminary evidence of a beneficial host proinflammatory and/or Ag-specific immune response. The Journal of Immunology, 2009, 183: 7428-7440.
引用
收藏
页码:7428 / 7440
页数:13
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