CD4+CD25+FoxP3+ T-cell infiltration and heme oxygenase-1 expression correlate with tumor grade in human gliomas

Andaloussi, Abdeljabar El; Lesniak, Maciej S.

doi:10.1007/s11060-006-9314-y

Cited by 122 publications

(97 citation statements)

References 36 publications

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“…BILs isolated from infected (Vacc) and noninfected (Non-Vacc) RasB8×129SvPas mice were analyzed 7 days after infection. IFN-γ expression gated on CD8 T cells is shown after ex vivo restimulation with phorbol 12-myristate 13-acetate/ionomycin (PMA-iono) or with a VV peptide (B8R [20][21][22][23][24][25][26][27] , TSYKFESV; B1). Quadrants in representative dot plots were defined according to isotype control staining.…”

Section: Discussionmentioning

confidence: 99%

“…eBiosciences (FoxP3 staining) or BD Biosciences (IFN-γ, tumor necrosis factor, interleukin 2, granzyme B) permeabilization and fixation kits were used according to the instructions of the manufacturer. Where indicated, cells were restimulated with phorbol 12-myristate 13-acetate and ionomycin in a monensin solution for 6 hours or with a VV peptide (B8R [20][21][22][23][24][25][26][27] , TSYKFESV). Live leukocytes were gated on scatter and analyzed using BD Bioscience or Beckman Coulter cytometers, and results processed with FlowJo software (Tree Star, Inc.).…”

Section: Flow Cytometrymentioning

confidence: 99%

“…Active immunosuppressive mechanisms in human gliomas include soluble factors such as transforming growth factor-β (18,19) and cell surface molecules (20,21). Several recent studies have focused on gliomainfiltrating immunosuppressive cells, of which Tregs are the best defined (22,23). However, the most abundant gliomainfiltrating cells are macrophages/activated microglia.…”

Section: Introductionmentioning

confidence: 99%

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Immune Infiltration of Spontaneous Mouse Astrocytomas Is Dominated by Immunosuppressive Cells from Early Stages of Tumor Development

et al. 2010

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Immune infiltration of advanced human gliomas has been shown, but it is doubtful whether these immune cells affect tumor progression. It could be hypothesized that this infiltrate reflects recently recruited immune cells that are immediately overwhelmed by a high tumor burden. Alternatively, if there is earlier immune detection and infiltration of the tumor, the question arises as to when antitumor competency is lost. To address these issues, we analyzed a transgenic mouse model of spontaneous astrocytoma (GFAP-V 12 HA-ras mice), which allows the study of immune interactions with developing glioma, even at early asymptomatic stages. T cells, including a significant proportion of Tregs, are already present in the brain before symptoms develop, followed later by macrophages, natural killer cells, and dendritic cells. The effector potential of CD8 T-cells is defective, with the absence of granzyme B expression and low expression of IFN-γ, tumor necrosis factor, and interleukin 2. Overall, our results show an early defective endogenous immune response to gliomas, and local accumulation of immunosuppressive cells at the tumor site. Thus, the antiglioma response is not simply overwhelmed at advanced stages of tumor growth, but is counterbalanced by an inhibitory microenvironment from the outset. Nevertheless, we determined that effector molecule expression (granzyme B, IFN-γ) by brain-infiltrating CD8 T-cells could be enhanced, despite this unfavorable milieu, by strong immune stimuli. This potential to modulate the strong imbalance in local antiglioma immunity is encouraging for the development and optimization of future glioma immunotherapies. Cancer Res; 70(12); 4829-39. ©2010 AACR.

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Section: Discussionmentioning

confidence: 99%

Section: Flow Cytometrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Immune Infiltration of Spontaneous Mouse Astrocytomas Is Dominated by Immunosuppressive Cells from Early Stages of Tumor Development

et al. 2010

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“…The heme oxygenase-1 seems to play a role in the immune suppressive phenotype of Tregs. Tumor infiltrating Tregs express heme oxygenase-1 and expression increased with tumor progression (El Andaloussi and Lesniak, 2007). The chemokines CCL2 and CCL22 are candidates as chemoattractant factors for Tregs (Jordan et al, 2008).…”

Section: Interaction Of T Lymphocytes With Gliomamentioning

confidence: 99%

The brain tumor microenvironment

Charles

Holland

Gilbertson

et al. 2011

Glia

693

327

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High-grade brain tumors are heterogeneous with respect to the composition of bona fide tumor cells and with respect to a range of intermingling parenchymal cells. Glioblastomas harbor multiple cell types, some with increased tumorigenicity and stem cell-like capacity. The stem-like cells may be the cells of origin for tumor relapse. However, the tumor-associated parenchymal cells such as vascular cells, microglia, peripheral immune cells, and neural precursor cells also play a vital role in controlling the course of pathology. In this review, we describe the multiple interactions of bulk glioma cells and glioma stem cells with parenchymal cell populations and highlight the pathological impact as well as signaling pathways known for these types of cell-cell communication. The tumor-vasculature not only nourishes glioblastomas, but also provides a specialized niche for these stem-like cells. In addition, microglial cells, which can contribute up to 30% of a brain tumor mass, play a role in glioblastoma cell invasion. Moreover, non-neoplastic astrocytes can be converted into a reactive phenotype by the glioma microenvironment and can then secrete a number of factors which influences tumor biology. The young brain may have the capacity to inhibit gliomagenesis by the endogenous neural precursor cells, which secrete tumor suppressive factors. The factors, pathways, and interactions described in this review provide a new prospective on the cell biology of primary brain tumors, which may ultimately generate new treatment modalities. However, our picture of the multiple interactions between parenchymal and tumor cells is still incomplete. V

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“…For instance, it was shown that FoxP3 expression correlates with the tumoral progression in several types of astrocytomas [193], and that temozolomide, the standard chemotherapeutic agent for glioblastoma, induced a reduction of Tregs, both in the blood and in the tumor tissues [194]. Therefore, Tregs have been identified as a novel targets in glioma treatment.…”

Section: Cns Pediatric Tumor Microenvironmentmentioning

confidence: 99%

In Vitro Modeling of Tissue-Specific 3D Microenvironments and Possibile Application to Pediatric Cancer Research

Pizzimenti¹

2014

J. Pediatr. Oncol.

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A large body of evidence indicates that three dimensional (3D) cancer models are superior to two-dimensional (2D) ones in better representing the in vivo phenomena. Indeed, 3D models allow recapitulating in vitro the in vivo features observed in solid tumors (e.g. cell polarity, cell-cell/cell-matrix interactions, biochemical/metabolic gradients, anchorage-independent growth and hypoxia). Moreover, it is well established that the microenvironment plays a fundamental role in regulating tumor development and behavior, including drug resistance. Thus, innovative models able to mimic this complexity represent attractive tools in cancer research. In this review article, we provide a comprehensive review of the application of 3D culture systems in pediatrics' cancer research. In particular, 3D in vitro/ex vivo models of the most common pediatric tumors, such as leukemias, lymphomas and malignancies of the nervous system, will be considered.

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CD4+CD25+FoxP3+ T-cell infiltration and heme oxygenase-1 expression correlate with tumor grade in human gliomas

Cited by 122 publications

References 36 publications

Immune Infiltration of Spontaneous Mouse Astrocytomas Is Dominated by Immunosuppressive Cells from Early Stages of Tumor Development

Immune Infiltration of Spontaneous Mouse Astrocytomas Is Dominated by Immunosuppressive Cells from Early Stages of Tumor Development

The brain tumor microenvironment

In Vitro Modeling of Tissue-Specific 3D Microenvironments and Possibile Application to Pediatric Cancer Research

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