Fas expression by tumor stroma is required for cancer eradication


  • J.J. Listopad
  • T. Kammertoens
  • K. Anders
  • B. Silkenstedt
  • G. Willimsky
  • K. Schmidt
  • A.A. Kuehl
  • C. Loddenkemper
  • T. Blankenstein


  • Proceedings of the National Academy of Sciences of the United States of America


  • Proc Natl Acad Sci U S A 110 (6): 2276-2281


  • 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.