title: Selective expression of inhibitory Fcgamma receptor by metastatic melanoma impairs tumor susceptibility to IgG-dependent cellular response.
abstract: During melanoma progression, patients develop anti-tumor immunity including the production of anti-tumor antibodies. Although the strategies developed by malignant cells to escape anti-tumor cellular immunity have been extensively investigated, little is known about tumor resistance to humoral immunity. The main effect of IgG antibodies is to activate the immune response by binding to host Fc gamma receptors (FcgammaR) expressed by immune cells. We previously reported in a limited study that some human metastatic melanoma cells ectopically express the FcgammaRIIB1, an inhibitory isoform of FcgammaR. By analyzing a large panel of different types of human primary and metastatic solid tumors, we report herein that expression of FcgammaRIIB is restricted to melanoma and is acquired during tumor progression. We show that FcgammaRIIB expression prevents the lysis of human metastatic melanoma cells by NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) in vitro, independently of the intracytoplasmic region of FcgammaRIIB. Using experimental mouse models, we demonstrate that expression of FcgammaRIIB protects B16F0 melanoma tumors from the ADCC induced by monoclonal and polyclonal anti-tumor IgG in vivo. Thus, our results identify FcgammaRIIB as a marker of human metastatic melanoma that impairs the tumor susceptibility to FcgammaR-dependent innate effector responses.
authors.affiliation: INSERM, U872, Microenvironnement immunitaire et tumeurs, Equipe 13, Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Cassard
authors.forename: Joel F G
authors.initials: JF
authors.lastname: Cohen-Solal
authors.forename: Emilie M
authors.initials: EM
authors.lastname: Fournier
authors.forename: Sophie
authors.initials: S
authors.lastname: Camilleri-Broët
authors.forename: Alain
authors.initials: A
authors.lastname: Spatz
authors.forename: Salem
authors.initials: S
authors.lastname: Chouaïb
authors.forename: Cécile
authors.initials: C
authors.lastname: Badoual
authors.forename: Audrey
authors.initials: A
authors.lastname: Varin
authors.forename: Sylvain
authors.initials: S
authors.lastname: Fisson
authors.forename: Pierre
authors.initials: P
authors.lastname: Duvillard
authors.forename: Charlotte
authors.initials: C
authors.lastname: Boix
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Loncar
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
authors.forename: Alan N
authors.initials: AN
authors.lastname: Houghton
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Avril
authors.forename: Ion
authors.initials: I
authors.lastname: Gresser
authors.forename: Wolf H
authors.initials: WH
authors.lastname: Fridman
authors.forename: Catherine
authors.initials: C
authors.lastname: Sautès-Fridman
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D045744:Cell Line, Tumor; D018450:Disease Progression; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007150:Immunohistochemistry; D008545:Melanoma / Q000276:immunology* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D017452:Receptors, IgG / Q000032:analysis*; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C080571:Fc gamma receptor IIB; D007074:Immunoglobulin G; D017452:Receptors, IgG