Abstract
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)-gamma production. Both, IL-10 production before and IFN-gamma production after Cy-treatment by TIMs required T cells. With the same kinetics as TIMs started to produce IFN-gamma the tumor vasculature was destroyed which required IFN-gamma 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents, Phytogenic / pharmacology*
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / immunology
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Cyclophosphamide / pharmacology*
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Fibrosarcoma / drug therapy
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Fibrosarcoma / immunology*
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Interferon gamma Receptor
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Interferon-gamma / biosynthesis
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Interferon-gamma / immunology
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Interleukin-10 / biosynthesis
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Lymphocytes, Tumor-Infiltrating
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Macrophages / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Mice, Nude
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Neoplasms, Experimental / drug therapy
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Neoplasms, Experimental / immunology
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Neovascularization, Pathologic / immunology
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Plasmacytoma / drug therapy
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Plasmacytoma / immunology*
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Receptors, Interferon / genetics
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Receptors, Interferon / immunology
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Stromal Cells / drug effects*
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Stromal Cells / immunology
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Time Factors
Substances
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Antineoplastic Agents, Phytogenic
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Receptors, Interferon
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Interleukin-10
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Interferon-gamma
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Cyclophosphamide