Vascular Endothelial Growth Factor Inhibits the Development of Dendritic Cells and Dramatically Affects the Differentiation of Multiple Hematopoietic Lineages In Vivo

Gabrilovich, Dmitry I.; Ishida, Tadao; Oyama, Tsunehiro; Ran, Sophia; Kravtsov, Vladimir; Nadaf, Sorena; Carbone, David P.

doi:10.1182/blood.v92.11.4150.423k45_4150_4166

Cited by 406 publications

(239 citation statements)

References 47 publications

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“…37 VEGF(165)-treated human adipose tissue showed significant cell proliferation and differentiated into muscle tissue and VEGF enhanced vascularization in this process. 38 Though there are some reports on the inhibition effects of VEGF on DC development, 31,32,39 little is known the effects of VEGF on the differentiation of DCs. It has been reported that iDCs developed into ELCs in the presence of VEGF, bFGF and IGF-1.…”

Section: Discussionmentioning

confidence: 99%

VEGF‐A‐induced immature DCs not mature DCs differentiation into endothelial‐like cells through ERK1/2‐dependent pathway

Lü

Zhao

et al. 2011

Cell Biochemistry & Function

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Dendritic cells (DCs) are professional antigen-presenting cells that play an important role in anti-tumour immunity. Endothelial-like differentiation of DCs is an interesting phenomenon. The specific role of vascular endothelial growth factor-A (VEGF-A) on the differentiation of immature DCs (iDCs) and mature DCs (mDCs) is worth further research. Here, we show that VEGF-A can induce iDCs to differentiate into endothelial-like cells (ELCs). But it has no obvious influence on mDCs. In the process of endothelial-like differentiation of iDCs, a sustained activation of extracellular signal-regulated kinase (ERK1/2) and cAMP response element binding protein (CREB) was detected. VEGF-A induced the activation of ERK1/2, and led to the nuclear translocation of phosphorylation ERK1/2. Incubation of iDCs with the ERK1/2 upstream kinase MEK1/2 inhibitor PD98059, blocked the phosphorylation of ERK1/2 and CREB as well as the endothelial-like differentiation of iDCs. These data suggest that VEGF-A induces endothelial-like differentiation of iDCs not mDCs through ERK1/2 signalling pathway.

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Section: Discussionmentioning

confidence: 99%

VEGF‐A‐induced immature DCs not mature DCs differentiation into endothelial‐like cells through ERK1/2‐dependent pathway

Lü

Zhao

et al. 2011

Cell Biochemistry & Function

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“…T cells can play a role in angiogenesis by delivering VEGF to inflammatory sites, and VEGF can augment proinflammatory T-cell differentiation (Mor et al, 2004). VEGF inhibits T-cell development in mice (Ohm et al, 2003), inhibits maturation of DC (Gabrilovich et al, 1998;Takahashi et al, 2004) and promotes the production of IL-6.…”

Section: Vascular Endothelial Growth Factormentioning

confidence: 99%

Immunodeficiency and immunotherapy in multiple myeloma

2007

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Summary Multiple myeloma is a malignant tumour of plasma cells that remains incurable for the vast majority of patients, with a median survival of 2–3 years. It is characterized by the patchy accumulation of tumour cells within bone marrow leading to variable anaemia, bone destruction, hypercalcaemia, renal failure and infections. Immune dysfunction is an important feature of the disease and leads to infections that are both a major cause of morbidity and mortality and may promote tumour growth and resistance to chemotherapy. Numerous defects of the immune system have been described in multiple myeloma although the relative clinical importance of these remains elusive. There has been considerable interest in the identification of an autologous response against myeloma. Although T cells and humoral responses directed against myeloma‐associated antigens have been described, it is uncertain if the immune system plays a role in preventing or controlling myeloma cell growth. There is increasing interest in the potential role of immunotherapy but the success of these interventions is likely to be modified by the immunologically hostile environment associated with multiple myeloma. This review attempts to summarize the current knowledge relating to the immune defects found in multiple myeloma.

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“…When MDSCS (CD11b + /Gr + cells) were co-injected with tumour cells, enhanced angiogenesis and tumour growth were noted with promotion of tumour resistance to anti-VEGF antibodies. In murine models, blocking VEGF decreased the number of suppressive cells encountered in the tumour (Gabrilovich et al, 1998) but this was not evident in a clinical study in humans using the anti-VEGF antibody Bevacizumab (Rodriguez et al, 2009).…”

Section: Pro-angiogenic Effectmentioning

confidence: 99%

“…One of these is the anti-VEGF antibody bevacizumab. Murine anti-VEGF was used successfully by Gabrilovich et al (1998), who showed that it had a positive therapeutic effect both on tumour blood vessels and the number of MDSCs present. However, in a clinical trial for patients with RCC, controversial results were reported after treatment with anti-VEGF antibody resulted in decreased levels of VEGF but had no effect on the numbers of MDSCs present (Rodriguez et al, 2009).…”

Section: Drugs Affecting Mdsc Functionmentioning

confidence: 99%

Myeloid‐derived suppressor cells – their role in haemato‐oncological malignancies and other cancers and possible implications for therapy

Tadmor

Attias

Polliack³

2011

Br J Haematol

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SummaryMyeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells at different stages of maturation that play a role in cancer tolerance and function as an immune-suppressive cell subpopulation. They utilize different mechanisms to block both innate and adaptive arms of anti-tumour immunity, mostly through inhibition of T cell activation and expansion. Further advances in our understanding of this cell population in both murine models and humans has enabled more accurate characterization of their phenotype and the recognition of two major classes of MDSCs: granulocytic and monocytic. Recently, the mechanism of action and clinical importance of MDSCs has been more clearly defined and their interactions with cancer cells have been shown to be among the factors influencing tumour development and induction of tolerance. Most of the earlier studies were performed using murine models, but recent clinical investigations have shown their potential role in human cancers. Here, we review the origin of MDSCs, their mechanisms of action, the factors influencing their production and related signalling pathways. We focus on their role in human solid tumours and haemato-oncological malignancies, and relate to possible novel therapeutic approaches targeting MDSCs which could be considered together with other anticancer strategies in the not too distant future.

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Vascular Endothelial Growth Factor Inhibits the Development of Dendritic Cells and Dramatically Affects the Differentiation of Multiple Hematopoietic Lineages In Vivo

Cited by 406 publications

References 47 publications

VEGF‐A‐induced immature DCs not mature DCs differentiation into endothelial‐like cells through ERK1/2‐dependent pathway

VEGF‐A‐induced immature DCs not mature DCs differentiation into endothelial‐like cells through ERK1/2‐dependent pathway

Immunodeficiency and immunotherapy in multiple myeloma

Myeloid‐derived suppressor cells – their role in haemato‐oncological malignancies and other cancers and possible implications for therapy

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