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Original Article

¹ Max-Delbrück-Center for Molecular Medicine, 13092 Berlin, Germany
² Institute of Immunology, Free University Berlin, 12200 Berlin, Germany

Address correspondence to Zhihai Qin, Institute of Immunology, Free University Berlin, Hindenburgdamm 30, 12200 Berlin, Germany. Phone: 49-30-94063196; Fax: 49-30-94062453; E-mail: zhihai{at}mdc-berlin.de

The stroma of solid tumors is a complex network of different cell types. We analyzed stroma cell interactions in two tumor models during cyclophosphamide (Cy)-induced tumor rejection. In growing tumors, tumor infiltrating macrophages (TIMs) produced interleukin (IL)-10. Beginning 6 h after Cy-treatment T cells in the tumor were inactivated and TIMs switched to interferon (IFN)- production. Both, IL-10 production before and IFN- production after Cy-treatment by TIMs required T cells. With the same kinetics as TIMs started to produce IFN- the tumor vasculature was destroyed which required IFN- receptor expression on host but not tumor cells. These events preceded hemorrhagic necrosis and residual tumor cell elimination by T cells. Together, T cells regulate the function of TIMs and tumor rejection can be induced by disturbing the stroma network.

Key Words: tumor stroma • tumor infiltrating macrophages • IFN- • antiangiogenesis • cyclophosphamid

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