Tumor rejection by disturbing tumor stroma cell interactions.
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.
Ibe
S
S
Max-Delbrück-Center for Molecular Medicine, 13092 Berlin, Germany.
Qin
Z
Z
Schüler
T
T
Preiss
S
S
Blankenstein
T
T
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003520:Cyclophosphamide / Q000494:pharmacology*; D005354:Fibrosarcoma / Q000188:drug therapy / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis; D016246:Lymphocytes, Tumor-Infiltrating; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology; D009389:Neovascularization, Pathologic / Q000276:immunology; D010954:Plasmacytoma / Q000188:drug therapy / Q000276:immunology*; D017471:Receptors, Interferon / Q000235:genetics / Q000276:immunology; D017154:Stromal Cells / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D000096743:Interferon gamma Receptor
D000972:Antineoplastic Agents, Phytogenic; D003520:Cyclophosphamide; D007371:Interferon-gamma; D016753:Interleukin-10; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor