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Escape from immune surveillance and promotion of tumor angiogenesis are essential for tumors to grow and progress. These two aspects are governed by the immune system and the angiogenic network of the host. In this report, we demonstrate a novel tumor-promoting role of myeloid immune suppressor Gr+CD11b+ cells, which are evident in cancer patients and tumor-bearing animals. These cells constitute approximately 5% of total cells in tumors. Tumors coinjected with Gr+CD11b+ cells exhibited increased vascular density, vascular maturation and decreased necrosis. These immune cells produce high levels of MMP9. Deletion of MMP9 in these cells completely abolishes their tumor-promoting ability. Gr+CD11b+ cells were also found to directly incorporate into tumor endothelium. Consistent with this observation, Gr+CD11b+ cells acquire endothelial cell (EC) properties in tumor microenvironment and proangiogenic culture conditions. Our data provide evidence that Gr+CD11b+ cells of immune origin induced by tumors directly contribute to tumor growth and vascularization by producing MMP9 and differentiating into ECs. The proangiogenic role of myeloid immune suppressor cells induced by tumors might constitute a critical mechanism by which tumors subvert their host. Interventions aimed at eliminating these cells may improve anti-tumor immune response and concurrently inhibit tumor angiogenesis.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]