Fas ligand breaks tolerance to self-antigens and induces tumor immunity mediated by antibodies.
The role of Fas ligand (FasL) in programmed cell death via interaction with its receptor Fas is well characterized. It has been proposed that expression of FasL can confer immune privilege to some organs, allowing them to kill infiltrating lymphocytes and inflammatory cells. However, a number of studies have shown that when tumors or transplants express FasL, rejection often occurs as a consequence of proinflammatory functions of FasL. Here we demonstrate that FasL elicits tumor immunity in a murine melanoma model with weak immunogenicity and low expression of major histocompatibility complex (MHC) class I. We show that protected mice recognize melanocyte differentiation self-antigens. Importantly, tumor immunity is mediated by antibodies, as it can be transferred by serum from protected mice.
Simon
Anna Katharina
AK
MRC Human Immunology Unit and Nuffield Department of Medicine, Institute of Molecular Medicine, OX3 9DS, Oxford, United Kingdom.
Gallimore
Awen
A
Jones
Emma
E
Sawitzki
Birgit
B
Cerundolo
Vincenzo
V
Screaton
Gavin R
GR
D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D003713:Dendritic Cells / Q000276:immunology; D018572:Disease-Free Survival; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins; D007108:Immune Tolerance; D007136:Immunoglobulins / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008164:Luminescent Proteins / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating; D008544:Melanocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000556:secondary; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D001324:Autoantigens; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007136:Immunoglobulins; D008070:Lipopolysaccharides; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D049452:Green Fluorescent Proteins