Responsiveness of Stromal Fibroblasts to IFN-γ Blocks Tumor Growth via Angiostasis

Abstract

The importance of stromal cells for tumor is akin to soil for seed. However, the interaction among these cells is far from understood. In this study, we show that stromal fibroblasts exist not only during tumor progression but also during regression stage, together with immune effector cells. Coinjection of stromal fibroblasts with tumor cells often promotes tumor growth. However, the presence of IFN-gamma significantly impairs the ability of these cells to promote tumor growth due to a reduced angiogenesis. The mechanism relies mainly on the IFN-gamma-mediated down-regulation of vascular endothelial growth factor production by fibroblasts. The results reveal a novel link between immune cells and nonbone marrow-derived stromal cells, and define stromal fibroblasts as the main targets of IFN-gamma in tumor immunity.