Decrease of VEGF-A in myeloid cells attenuates glioma progression and prolongs survival in an experimental glioma model

Osterberg, Nadja; Ferrara, Napoleone; Vacher, Jean; Gaedicke, Simone; Niedermann, Gabriele; Weyerbrock, Astrid; Doostkam, Soroush; Schaefer, Hans-Eckart; Plate, Karl H.; Machein, Márcia Regina

doi:10.1093/neuonc/now005

Cited by 43 publications

(34 citation statements)

References 37 publications

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“…Nevertheless, another promising therapeutic approach for the treatment of glioblastoma consists in the use of nanoparticles which are internalized by GAMs increasing their antitumor immune activation [79,80] . Moreover, GAMs produce a vast array of growth and angiogenic factors which further sustain proliferation of tumor cells [8,48,52] as well as tumor vessel formation [81] . Interestingly, genetic and pharmacological ablation in GAMs of neuropilin 1, a co-receptor that amplifies signaling through the VEGF-A and TGFβ pathways, is associated with reduced glioma growth and blood vessel formation and increased survival time of glioma bearing mice [82] .…”

Section: Other Features Of Gamsmentioning

confidence: 99%

Glioma associated microglia/macrophages, a potential pharmacological target to promote antitumor inflammatory immune response in the treatment of glioblastoma

Russo¹,

Cappoli²

2018

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Glioma associated microglia/macrophages (GAMs) constitute the largest proportion of glioma infiltrating cells, particularly in high grade tumors (i.e., glioblastoma). Once inside the tumors, GAMs usually acquire a specific phenotype of activation that favors tumor growth, angiogenesis and promotes the invasion of normal brain parenchyma. Therefore, treatments that limit or prevent GAMs' recruitment at the tumor site or modulate their immune activation promoting antitumor activities are expected to exert beneficial effects in glioblastoma. In the present paper, we aim at the revision of pharmacological strategies that interfere with GAMs' function and are currently proposed as an alternative/additional option to current approved cytotoxic regimens.

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Section: Other Features Of Gamsmentioning

confidence: 99%

Glioma associated microglia/macrophages, a potential pharmacological target to promote antitumor inflammatory immune response in the treatment of glioblastoma

Russo¹,

Cappoli²

2018

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“…Here, microglia/macrophages were assumed as one reason for this circumstance due to their increased accumulation following anti‐angiogenic treatment (Lu‐Emerson et al, ; Piao et al, ). Additionally, VEGF is able to mobilize blood monocytes and microglia cell lines in vitro (Forstreuter, Lucius, & Mentlein, ; Kerber et al, ), and microglia/macrophages themselves produce VEGF (Brandenburg et al, ; X. Chen et al, ) that is conducive to glioma progression (Osterberg et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, VEGF is able to mobilize blood monocytes and microglia cell lines in vitro (Forstreuter, Lucius, & Mentlein, 2002;Kerber et al, 2008), and microglia/macrophages themselves produce VEGF (Brandenburg et al, 2016;X. Chen et al, 2014) that is conducive to glioma progression (Osterberg et al, 2016).…”

mentioning

confidence: 99%

VEGF as a modulator of the innate immune response in glioblastoma

Turkowski

Brandenburg

Mueller

et al. 2017

Glia

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VEGF is an important factor in tumor vascularization and used as target for anti-angiogenic treatment strategies in glioma. In this study, we demonstrate for the first time that VEGF is a modulator of the innate immune response with suppressive effects on the immunologic and proangiogenic function of microglia/macrophages in a glioblastoma rodent model. High level of VEGF led to threefold enlarged tumor volumes and a pronounced remodeling of the vascular structure along with a reduced infiltration of microglia/macrophages by approximately 50%. Remaining microglia/macrophages showed an enhanced rate of apoptosis as well as significant downregulation of the VEGF-receptor, VEGFR2, and others such as CXCR4. Consequently, we determined a substantially impaired migration of these microglia/macrophages to VEGF and SDF1a in vitro. Furthermore, we observed an increased presentation of the surface molecules MHCI and MHCII on microglia/macrophages from VEGF-overexpressing gliomas that are essential for activation of the adaptive immune system. In contrast, the expression of pro-inflammatory and suppressive cytokines, associated with the innate immune response, were mainly downregulated. Remarkably, the abundance of VEGF provoked less accumulation of microglia/macrophages within the perivascular niche and concomitantly reduced the release of pro-angiogenic factors, like VEGF, suggesting a possible regulatory feedback mechanism. Thus, the quantity of VEGF in the glioma microenvironment seems to be crucial for the participation of microglia/macrophages on tumor progression and should be considered for developing novel therapeutic approaches. K E Y W O R D SGBM, microglia/macrophages, SDF1a, tumor angiogenesis, VEGFR2

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“…Vascular epithelial growth factor A (VEGF-A) is a pro-angiogenic cytokine released by M2-like TAMs, and high VEGF-A levels correlate with TAM density in various cancers [80,83]. Moreover, TAM-derived VEGF contributes to tumor neovascularization [84,85]. In breast cancer, TAM-secreted wingless-type MMTV integration site family, member 7B (WNT7b) increased VEGF-A expression in vascular endothelial cells to promote angiogenesis [86].…”

Section: Tams In Angiogenesismentioning

confidence: 99%

Contribution of Macrophages and T Cells in Skeletal Metastasis

Mendoza-Reinoso

McCauley

Fournier

2020

Cancers

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Bone is a common site for metastases with a local microenvironment that is highly conducive for tumor establishment and growth. The bone marrow is replete with myeloid and lymphoid linage cells that provide a fertile niche for metastatic cancer cells promoting their survival and growth. Here, we discuss the role of macrophages and T cells in pro- and anti-tumoral mechanisms, their interaction to support cancer cell growth, and their contribution to the development of skeletal metastases. Importantly, immunotherapeutic strategies targeting macrophages and T cells in cancer are also discussed in this review as they represent a great promise for patients suffering from incurable bone metastases.

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Decrease of VEGF-A in myeloid cells attenuates glioma progression and prolongs survival in an experimental glioma model

Abstract: Our results highlight the importance of VEGF derived from tumor-infiltrating myeloid cells for initiating vascularization in gliomas. The combination of antiangiogenic agents with myeloid cell-targeting strategies might provide a new therapeutic approach for glioblastoma patients.

Cited by 43 publications

References 37 publications

Glioma associated microglia/macrophages, a potential pharmacological target to promote antitumor inflammatory immune response in the treatment of glioblastoma

Glioma associated microglia/macrophages, a potential pharmacological target to promote antitumor inflammatory immune response in the treatment of glioblastoma

VEGF as a modulator of the innate immune response in glioblastoma

Contribution of Macrophages and T Cells in Skeletal Metastasis

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