CD4+ T cell--mediated tumor rejection involves inhibition of angiogenesis that is dependent on IFN gamma receptor expression by nonhematopoietic cells.
Immunity against MHC class II tumors can be mediated by CD4+ T cells in the effector phase through an unknown mechanism. We show that this is IFN gamma dependent but does not require IFN gamma receptor (IFN gamma R) expression on tumor cells, T cells, or other hematopoietic cells and that IFN gamma R expression is not necessary in the priming phase. However, tumor immunity requires IFN gamma R expression on nonhematopoietic cells in the effector phase and involves inhibition of tumor-induced angiogenesis. This shows that an effective anti-tumor response involves communication between CD4+ T cells and nonhematopoietic cells, most likely within the tumor stroma, and that tumor immunity must not entirely rely on direct tumor cell killing.
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Max-Delbrück-Center for Molecular Medicine, Berlin, Germany. zhihai@mdc-berlin.de
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D020533:Angiogenesis Inhibitors / Q000502:physiology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002474:Cell-Free System / Q000502:physiology; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D006131:Growth Inhibitors / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D017471:Receptors, Interferon / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014407:Tumor Cells, Cultured; D000096743:Interferon gamma Receptor
D020533:Angiogenesis Inhibitors; D006131:Growth Inhibitors; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor