cancer [62,63]. CXC chemokines are

cancer [62,63]. CXC chemokines are thought to stimulate themigration of neutrophils across the vasculature to recruit into thetumors [63,64]. Several in vivo studies using various models ofangiogenesis have clearly shown that neutrophils induce neovascularization processes. The depletion of Gr1 mediated neutrophils hasbeen demonstrated to strongly reduce angiogenesis in Matrigel withCXCL1 or CXCL8 compared to controls [65]. Furthermore, theinfiltrating neutrophils have a crucial role in activating angiogenesisduring the early stage of carcinogenesis [66]. It has been shown thatthe transient depletion of neutrophils could significantly suppressVEGF and thus remarkably reduces the frequency of the initialangiogenic switch, as tumor infiltrating neutrophils along withmacrophages are two major sources of MMP9 in the angiogenicstages of pancreatic islet carcinogenesis [66].Increased levels of eosinophils, another subpopulation of whiteblood cells, have been found in human tumors [67]. How eosinophilscontribute to angiogenesis in vivo is still not completely understood.Eosinophil infiltration probably induces angiogenic responses in vivothrough the production of CCL11 [68]. Also mast cells originate fromthe BM and circulate as immature cells and migrate to tissues wherethey finally mature. They recruit into tumors and are frequently foundin close contact with blood vessels within the tumor microenvironment [69]. Increased numbers of mast cells have been observed invarious tumors, and increased mast cell density correlates positivelywith increased microvessel density in many human tumors [70]. Theimportance of mast cells for tumor angiogenesis has been addressedby several studies. The angiogenic response to implanted B16-BL6melanoma in mast cell deficient W/Wv mice was showed to be slowerand less intense than in the wild type mice [71], and with bonemarrow repair of the mast cell deficiency, angiogenic response couldbe fully restored [71]. Furthermore, mast cells are also a rich source ofpreformed angiogenic cytokines and growth factors, such as VEGF,bFGF, MMP9, and IL-6 [72]. The degranulation of tumor associatedmast cells might be releasing these proangiogenic factors within thetumor microenvironment and thus promoting angiogenesis.Dendritic cells (DCs) are crucial regulators of adaptive immuneresponses and are viewed as the major professional antigen presenting cells (APC), with a unique ability to induce both primary andsecondary T- and B-cell responses, as well as immune tolerance [73].Gabrilovich et al. [54] identified VEGF as a factor which influences DCmaturation without affecting the function of relatively mature DCs invitro. Tumor-derived factors, such as VEGF, might be restricting thematuration of myeloid dendritic cells (DCs) and their subsequentaccumulation to tumor tissues. Some in vivo studies have shown thattumor DCs also possess proangiogenic properties [74]. Tumorassociated plasmacytoid dendritic cells could induce angiogenesisby producing TNFα and IL-8, while myeloid dendritic cells wereabsent from malignant ascites [74].