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Fas expression by tumor stroma is required for cancer eradication

Item Type:Article
Title:Fas expression by tumor stroma is required for cancer eradication
Creators Name:Listopad, J.J. and Kammertoens, T. and Anders, K. and Silkenstedt, B. and Willimsky, G. and Schmidt, K. and Kuehl, A.A. and Loddenkemper, C. and Blankenstein, T.
Abstract:The contribution of molecules such as perforin, IFN-{gamma} (IFN{gamma}), 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 IFN{gamma} on tumor stroma cells to avoid selection of antigen-loss variants. Because "cancer-driving" antigens (CDAs) are rarely counterselected, IFN{gamma} 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 IFN{gamma} or FasL could not prevent relapse despite retention of the rejection antigen by the cancer cells. Complete tumor rejection required IFN{gamma}-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.
Keywords:T-Cell Therapy, Immune Escape, Animals, Mice
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:110
Number:6
Page Range:2276-2281
Date:5 February 2013
Official Publication:https://doi.org/10.1073/pnas.1218295110
PubMed:View item in PubMed

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