Treg depletion with a low-dose metronomic temozolomide regimen in a rat glioma model

Banissi, Claire; Ghiringhelli, François; Chen, Lin; Carpentier, Antoine F.

doi:10.1007/s00262-009-0671-1

Cited by 210 publications

(182 citation statements)

References 25 publications

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“…The brain environment plays an important role since this correlation was not observed in gliomas injected subcutaneously (Biollaz et al, 2009). Low-dose application of Temozolomide, the standard chemotherapeutic agent for glioblastoma, reduced the number of circulating Tregs and induced a slight and nearly significant decrease in the percentage of Treg within the tumor (Banissi et al, 2009). Thus Tregs associated with glioma represent a novel target for glioma therapy.…”

Section: Interaction Of T Lymphocytes With Gliomamentioning

confidence: 99%

The brain tumor microenvironment

Charles

Holland

Gilbertson

et al. 2011

Glia

683

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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Section: Interaction Of T Lymphocytes With Gliomamentioning

confidence: 99%

The brain tumor microenvironment

Charles

Holland

Gilbertson

et al. 2011

Glia

683

327

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show abstract

“…78 Moreover, metronomic temozolomide, an analog of dacarbazine, reduced the number and the suppressive function of circulating Tregs in rats bearing glioma, although it did not restrain tumor growth. 79 The role of CTX on MDSCs is more controversial. Early reports have supported the concept that CTX induces the development of natural suppressor cells.…”

Section: Effects On Regulatory Subsets and Pathwaysmentioning

confidence: 99%

Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer

et al. 2013

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Conventional anticancer chemotherapy has been historically thought to act through direct killing of tumor cells. This concept stems from the fact that cytotoxic drugs interfere with DNA synthesis and replication. Accumulating evidence, however, indicates that the antitumor activities of chemotherapy also rely on several off-target effects, especially directed to the host immune system, that cooperate for successful tumor eradication. Chemotherapeutic agents stimulate both the innate and adaptive arms of the immune system through several modalities: (i) by promoting specific rearrangements on dying tumor cells, which render them visible to the immune system; (ii) by influencing the homeostasis of the hematopoietic compartment through transient lymphodepletion followed by rebound replenishment of immune cell pools; (iii) by subverting tumor-induced immunosuppressive mechanisms and (iv) by exerting direct or indirect stimulatory effects on immune effectors. Among the indirect ways of immune cell stimulation, some cytotoxic drugs have been shown to induce an immunogenic type of cell death in tumor cells, resulting in the emission of specific signals that trigger phagocytosis of cell debris and promote the maturation of dendritic cells, ultimately resulting in the induction of potent antitumor responses. Here, we provide an extensive overview of the multiple immune-based mechanisms exploited by the most commonly employed cytotoxic drugs, with the final aim of identifying prerequisites for optimal combination with immunotherapy strategies for the development of more effective treatments against cancer.

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“…One study found that Tregs isolated from patients with GBM had higher expression of a CCL2 receptor (CCR4) than did Tregs from normal patients (Jordan et al, 2008) suggesting that CCL2 expressed by GBM may be the chemoattractant for Tregs migration. In an experimental rodent model of glioma, treatment with a low dose of temozolomide resulted in a decreased level of Tregs infiltration and longer survival (Banissi et al, 2009). Indeed, the literature is lacking in studies that investigate whether temozolomide has a direct or indirect effect on other stromal cell types or their products and whether these effects induce a glioma inhibitory or glioma-promoting response.…”

Section: Temozolomidementioning

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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Treg depletion with a low-dose metronomic temozolomide regimen in a rat glioma model

Abstract: A low-dose metronomic TMZ regimen, but not a standard TMZ regimen, reduced the number of circulating Tregs. These results can have clinical applications for immunotherapeutic approaches in GBM.

Cited by 210 publications

References 25 publications

The brain tumor microenvironment

The brain tumor microenvironment

Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer

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

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