Abstract
Decreased immune function in cancer patients is well-characterized (1), and tumor cells have developed a variety of mechanisms to avoid anti-tumor immune responses (2-8). One mechanism for inhibition of immune cell function by tumors is the production of soluble factors, such as IL- 10, TNF, TGF-beta, and Vascular Endothelial Growth Factor (VEGF). The effects of these factors appear to be twofold: To inhibit effector function and to impair the development of immune cells by acting on earlier stages of immunopoiesis. Immune suppression by tumors is accomplished by a variety of cellular and molecular mechanisms, and virtually all branches of the immune system can be affected. VEGF and its receptors have profound effects on the early development and differentiation of both vascular endothelial and hematopoetic progenitors (9). It induces proliferation of mature endothelial cells and is an important component in the formation of tumor neovasculature (10). VEGF is abundantly expressed by a large percentage of solid tumors and this over-expression is closely associated with a poor prognosis (11,12). Some of the earliest hematopoetic progenitors express receptors for VEGF (13), and we have demonstrated that VEGF causes a defect in the functional maturation of dendritic cells (DC) from progenitors. This developmental defect is associated with impaired activation of NF-kappaB (14-17). This review describes research demonstrating that VEGF is not only important for tumor vascularization, but is also a key factor produced by solid tumors to inhibit recognition and destruction of tumor cells by the immune system.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Antibodies, Monoclonal / pharmacology
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Antibodies, Monoclonal / therapeutic use
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Biological Factors / pharmacology
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Cell Differentiation
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Cells, Cultured / drug effects
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Cytokines / physiology
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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Dendritic Cells / pathology
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Endothelial Growth Factors / metabolism
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Endothelial Growth Factors / pharmacology
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Endothelial Growth Factors / physiology*
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Endothelium, Vascular / drug effects
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Gene Expression Regulation, Neoplastic / drug effects
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Hematopoiesis / drug effects
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Humans
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Immune Tolerance / drug effects
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Immunologic Deficiency Syndromes / etiology*
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Immunologic Deficiency Syndromes / immunology
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Immunologic Deficiency Syndromes / metabolism
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Immunologic Surveillance
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Immunotherapy
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Lymphokines / metabolism
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Lymphokines / pharmacology
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Lymphokines / physiology*
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Models, Immunological
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NF-kappa B / antagonists & inhibitors
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Neoplasm Proteins / metabolism
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Neoplasm Proteins / pharmacology
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Neoplasm Proteins / physiology*
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Neoplasms / blood supply
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Neoplasms / complications
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Neoplasms / immunology*
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Neoplasms / metabolism
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Neoplasms / therapy
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Neoplasms, Experimental / immunology
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Neovascularization, Pathologic / metabolism
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Receptor Protein-Tyrosine Kinases / drug effects
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Receptor Protein-Tyrosine Kinases / physiology
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Receptors, Growth Factor / drug effects
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Receptors, Growth Factor / physiology
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Receptors, Vascular Endothelial Growth Factor
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Self Tolerance
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Signal Transduction / drug effects
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
Substances
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Antibodies, Monoclonal
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Biological Factors
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Cytokines
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Endothelial Growth Factors
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Lymphokines
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NF-kappa B
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Neoplasm Proteins
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Receptors, Growth Factor
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Receptor Protein-Tyrosine Kinases
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Receptors, Vascular Endothelial Growth Factor