title: Fas expression by tumor stroma is required for cancer eradication.
abstract: The contribution of molecules such as perforin, IFN-γ (IFNγ), and particularly Fas ligand (FasL) by transferred CD8(+) effector T (T(E)) cells to rejection of large, established tumors is incompletely understood. Efficient attack against large tumors carrying a surrogate tumor antigen (mimicking a "passenger" mutation) by T(E) cells requires action of IFNγ on tumor stroma cells to avoid selection of antigen-loss variants. Because "cancer-driving" antigens (CDAs) are rarely counterselected, IFNγ may be expected to be dispensable in elimination of cancers by targeting a CDA. Here, initial regression of large, established tumors required neither IFNγ, FasL, nor perforin by transferred CD8(+) T(E) cells targeting Simian Virus (SV) 40 large T as CDA. However, cytotoxic T(E) cells lacking IFNγ or FasL could not prevent relapse despite retention of the rejection antigen by the cancer cells. Complete tumor rejection required IFNγ-regulated Fas by the tumor stroma. Therefore, T(E) cells lacking IFNγ or FasL cannot prevent progression of antigenic cancer because the tumor stroma escapes destruction if its Fas expression is down-regulated.
authors: Max Delbrück Center for Molecular Medicine, 13125 Berlin,  Germany.
authors: Joanna J
authors: JJ
authors: Listopad
authors: Thomas
authors: T
authors: Kammertoens
authors: Kathleen
authors: K
authors: Anders
authors: Bjoern
authors: B
authors: Silkenstedt
authors: Gerald
authors: G
authors: Willimsky
authors: Karin
authors: K
authors: Schmidt
authors: Anja A
authors: AA
authors: Kuehl
authors: Christoph
authors: C
authors: Loddenkemper
authors: Thomas
authors: T
authors: Blankenstein
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D053222:Fas Ligand Protein / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D052899:Pore Forming Cytotoxic Proteins / Q000378:metabolism; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000276:immunology / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019014:fas Receptor / Q000378:metabolism*; D000096743:Interferon gamma Receptor
chemical_list: D053222:Fas Ligand Protein; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma; D052899:Pore Forming Cytotoxic Proteins; D017471:Receptors, Interferon; D019014:fas Receptor; D000096743:Interferon gamma Receptor; C491899:Fas protein, mouse; C505658:Fasl protein, mouse; C483886:perforin, mouse