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VEGF as a mediator of tumor-associated immunodeficiency

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Abstract

Decreased immune function in cancer patients is well-characterized (I), 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 in the production of soluble factors, such as IL-10, TNF, TGF-β, and Vascular Endothelial Growth Factor (VEGF). The effects of these factors appear, to be twofold: To inhibit effect or 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-κB (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.

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Authors and Affiliations

  1. Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 648 Medical Research Buikling II Nashville, TN, 37232, Nashville, TN

    Joyce E. Ohm &  David P. Carbone M.D., Ph.D.

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  1. Joyce E. Ohm
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  2. David P. Carbone M.D., Ph.D.
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Correspondence to David P. Carbone M.D., Ph.D..

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Ohm, J.E., Carbone, D.P. VEGF as a mediator of tumor-associated immunodeficiency. Immunol Res 23, 263–272 (2001). https://doi.org/10.1385/IR:23:2-3:263

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