title: Fas Ligand Deficiency Impairs Tumor Immunity by Promoting an Accumulation of Monocytic Myeloid-Derived Suppressor Cells.
abstract: The Fas receptor ligand FasL regulates immune cell levels by inducing apoptosis of Fas receptor-positive cells. Here, we studied the impact of host FasL on tumor development in mice. Genetically targeting FasL in naïve mice increased myeloid cell populations, but, in marked contrast, it reduced the levels of myeloid-derived suppressor cells (MDSC) in mice bearing Lewis lung carcinoma tumors. Analysis of the MDSC subset distribution revealed that FasL deficiency skewed cell populations toward the M-MDSC subset, which displays a highly immunosuppressive activity. Furthermore, tumor-bearing mice that were FasL-deficient displayed an enhanced proportion of tumor-associated macrophages and regulatory T cells. Overall, the immunosuppressive environment produced by FasL targeting correlated with reduced survival of tumor-bearing mice. These results disclose a new role for FasL in modulating immunosuppressive cells.
authors.affiliation: INSERM U753, Gustave Roussy Campus, Villejuif, France; Faculty of Medicine, University Paris Sud, Le Kremlin-Bicêtre, France.
authors.forename: Sanam
authors.initials: S
authors.lastname: Peyvandi
authors.affiliation: INSERM U753, Gustave Roussy Campus, Villejuif, France; Faculty of Medicine, University Paris Sud, Le Kremlin-Bicêtre, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Buart
authors.affiliation: INSERM U753, Gustave Roussy Campus, Villejuif, France; Faculty of Medicine, University Paris Sud, Le Kremlin-Bicêtre, France.
authors.forename: Boubekeur
authors.initials: B
authors.lastname: Samah
authors.affiliation: INSERM U753, Gustave Roussy Campus, Villejuif, France; Faculty of Medicine, University Paris Sud, Le Kremlin-Bicêtre, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Vétizou
authors.affiliation: INSERM U1170, Gustave Roussy Campus, Villejuif, France; University Paris Sud Faculty of Medicine, Le Kremlin-Bicêtre, France.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: INSERM U753, Gustave Roussy Campus, Villejuif, France; Faculty of Medicine, University Paris Sud, Le Kremlin-Bicêtre, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Durrieu
authors.affiliation: Preclinical Evaluation Platform (PFEP), Gustave Roussy Campus, Villejuif, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Polrot
authors.affiliation: INSERM U753, Gustave Roussy Campus, Villejuif, France; Faculty of Medicine, University Paris Sud, Le Kremlin-Bicêtre, France.
authors.forename: Salem
authors.initials: S
authors.lastname: Chouaib
authors.affiliation: CNRS UMR 8203, Gustave Roussy Campus, Villejuif, France; University Paris-Sud, Orsay, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Benihoud
authors.affiliation: INSERM U1170, Gustave Roussy Campus, Villejuif, France; University Paris Sud Faculty of Medicine, Le Kremlin-Bicêtre, France.
authors.forename: Fawzia
authors.initials: F
authors.lastname: Louache
authors.affiliation: INSERM U753, Gustave Roussy Campus, Villejuif, France; Faculty of Medicine, University Paris Sud, Le Kremlin-Bicêtre, France. saoussen.karray@inserm.fr.
authors.forename: Saoussen
authors.initials: S
authors.lastname: Karray
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D060890:B7-H1 Antigen / Q000378:metabolism; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000172:deficiency*; D006801:Humans; D056747:Immunomodulation; D016130:Immunophenotyping; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D047368:Tumor Burden / Q000235:genetics; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D060890:B7-H1 Antigen; D015415:Biomarkers; D053222:Fas Ligand Protein; D061026:Programmed Cell Death 1 Receptor