Profiling of CD4+, CD8+, and CD4+CD25+CD45RO+FoxP3+ T cells in patients with malignant glioma reveals differential expression of the immunologic transcriptome compared with T cells from healthy volunteers.
Clin Cancer Res
; 12(24): 7306-15, 2006 Dec 15.
Article
in En
| MEDLINE
| ID: mdl-17189402
ABSTRACT
PURPOSE:
Analyses of T-cell mRNA expression profiles in glioblastoma multiforme has not been previously reported but may help to define and characterize the immunosuppressed phenotype in patients with this type of cancer. EXPERIMENTALDESIGN:
We did microarray studies that have shown significant and fundamental differences in the expression profiles of CD4(+) and CD8(+) T cells and immunosuppressive CD4(+)CD25(+)CD45RO(+)FoxP3(+) regulatory T cells (T(reg)) from normal healthy volunteers compared with patients with newly diagnosed glioblastoma multiforme. For these investigations, we isolated total RNA from enriched CD4(+) and CD8(+) T cell or T(reg) cell populations from age-matched individuals and did microarray analyses.RESULTS:
ANOVA and principal components analysis show that the various T cell compartments exhibit consistently similar mRNA expression profiles among individuals within either healthy or brain tumor groups but reflect significant differences between these groups. Compared with healthy volunteers, CD4(+) and CD8(+) T cells from patients with glioblastoma multiforme display coordinate down-regulation of genes involved in T cell receptor ligation, activation, and intracellular signaling. In contrast, T(regs) from patients with glioblastoma multiforme exhibit increased levels of transcripts involved in inhibiting host immunity.CONCLUSION:
Our findings support the notion that key differences between expression profiles in T-cell populations from patients with glioblastoma multiforme results from differential expression of the immunologic transcriptome, such that a limited number of genes are principally important in producing the dysregulated T-cell phenotype.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain Neoplasms
/
T-Lymphocytes
/
CD4-Positive T-Lymphocytes
/
Leukocyte Common Antigens
/
CD8-Positive T-Lymphocytes
/
Forkhead Transcription Factors
/
Interleukin-2 Receptor alpha Subunit
/
Glioma
Type of study:
Observational_studies
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Clin Cancer Res
Journal subject:
NEOPLASIAS
Year:
2006
Type:
Article
Affiliation country:
United States