Immune defects observed in patients with primary malignant brain tumors

Dix, Amy R.; Brooks, William H.; Roszman, Thomas L.; Morford, Lorri A.

doi:10.1016/s0165-5728(99)00203-9

Cited by 289 publications

(208 citation statements)

References 183 publications

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“…Patients with glioblastoma multiforme typically exhibit a comprehensive and severe suppression of their immune system, which serves to dysregulate T-cell number, phenotype, or both (24). Cutaneous anergy, lymphopenia, impaired antibody production, reduced lymphocyte protein synthesis, and diminished lymphocyte responsiveness have all been reported (25 -33).…”

Section: Discussionmentioning

confidence: 99%

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

Learn¹,

Fecci²,

Schmittling³

et al. 2006

Clinical Cancer Research

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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. Experimental Design: 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 + Tcell 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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Learn¹,

Fecci²,

Schmittling³

et al. 2006

Clinical Cancer Research

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show abstract

“…Indeed it is possible that they may be subverted by the tumour into secreting factors that support glioma growth (Mantovani et al, 1992). Although transforming growth factor-β (TGF-β) produced by gliomas has been suggested to have a T-cell immunosuppressant role, the concentration of TGF-β in culture supernatants obtained from tumours does not correlate with the concentrations of TGF-β required to inhibit T-cell function in vitro (Dix et al, 1999). Although gliomas are infiltrated by lymphocytes to varying degrees, it has been reported that glioma-infiltrating lymphocytes are inactivated (Black et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

“…Glioma patients are known to have a depressed immune system (Dix et al, 1999). The nature of this immunodeficiency is complex and incompletely understood, but apoptosis of tumourinfiltrating lymphocytes may be a significant factor.…”

Section: Introductionmentioning

confidence: 99%

T-cell apoptosis in human glioblastoma multiforme: Implications for immunotherapy

Walker

Chuah

Rist

et al. 2006

Journal of Neuroimmunology

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We used immunohistochemistry and flow cytometry to assess apoptosis in human glioblastoma multiforme (GBM). Our immunohistochemical study revealed apoptosis of glioma cells expressing glial fibrillary acidic protein and of CD3 + T cells infiltrating GBM. To quantify and phenotype the apoptotic T cells, we performed flow cytometry on lymphocytes separated from GBM. The cells were stained with annexin-V-FLUOS/propidium iodide to identify apoptosis. We found that high proportions of both the CD4 + and CD8 + T cells were apoptotic. In particular, we found that T cells expressing Fas ligand (Fas-L, CD95L) were eight times more vulnerable to apoptosis than those not expressing Fas-L, which suggests that the Tcell apoptosis is induced by overactivation of the T-cell receptor, possibly in the absence of appropriate costimulation. Our results have implications for the design of immunotherapies for GBM.

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“…However, the potential contribution of microglia produced NO to the tumor stem cell phenotype that has yet to be explored. It has also been shown that glioma stem-like cells express multi-drug resistance proteins such as ABCG2 and P-gp (Lu and Shervington, 2008;Bleau et al, 2009;Wang et al, 2010); hence, these cells tend to be highly resistant to cytotoxic drug therapy (Charles and Holland, 2009 (Dix et al, 1999). Signaling through CXCL12-CXCR4 is known to recruit Tregs to bone marrow and may also be involved in the recruitment of Tregs to brain tumors (Zhou et al, 2002;Grauer et al, 2007).…”

Section: Glioma Stem-like Cellsmentioning

confidence: 99%

Standard of care therapy for malignant glioma and its effect on tumor and stromal cells

Jones

Holland

2011

Oncogene

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Immune defects observed in patients with primary malignant brain tumors

Cited by 289 publications

References 183 publications

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

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

T-cell apoptosis in human glioblastoma multiforme: Implications for immunotherapy

Standard of care therapy for malignant glioma and its effect on tumor and stromal cells

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