VEGF as a Mediator of tumor-associated immunodeficiency

Decreased immune function in cancer patients is well-characterized (I), and tumor cells have developed a variety of mechanisms to avoid anti-tumor imm une responses (2-8). One mechanism Ibr inhibition of immune cell function b y tumors is the production of soluble factors, such as IL-10, TNF TGF-beta, and Vascular Endothelial Growth Factor (VEGF). The effects of these factor s appear to be twofold: To inhibit effector function and to impair the deve lopment of immune cells by acting on earlier stages of immunopoiesis. Immun e suppression by tumors is accomplished by a variety of cellular and molecu lar mechanisms, and virtually all branches of the immune system can be affe cted. VEGF and its receptors have profound effects on the early development and differentiation of both vascular endothelial and hematopoetic progenit ors (9). It induces proliferation of mature endothelial cells and is an imp ortant component in the formation of tumor neovasculature (10). VEGF is abu ndantly expressed by a large percentage of solid tumors and this over-expre ssion is closely associated with a poor prognosis (11,12). Some of the earl iest hematopoetic progenitors express receptors for VEGF (13), and we have demonstrated that VEGF causes a defect in the Functional maturation of dend ritic cells (DC) from progenitors. This developmental defect is associated with impaired activation of NF-kappaB (14-17). This review describes resear ch demonstrating that VEGF is not only important for tumor vascularization, but is also a key factor produced by solid tumors to inhibit recognition a nd destruction of tumor cells by the immune system.