title: Modulation of tumor growth by inhibitory Fc(gamma) receptor expressed by human melanoma cells.
abstract: The efficacy of anti-tumor IgG reflects the balance between opposing signals mediated by activating and inhibitory Fc(gamma) receptors (Fc(gamma)Rs) expressed by effector cells. Here, we show that human malignant melanoma cells express the inhibitory low-affinity Fc(gamma) receptor Fc(gamma)RIIB1 in 40% of tested metastases. When melanoma cells were grafted in nude mice, a profound inhibition of Fc(gamma)RIIB1 tumor growth that required the intracytoplasmic region of the receptor was observed. IgG immune complexes (ICs) may be required for this inhibition, since sera from nude mice bearing tumors contained IgG that decreased the proliferation of Fc(gamma)RIIB1-positive cells in vitro, and tumor development of Fc(gamma)RIIB1-positive melanoma lines was not inhibited in antibody-defective severe combined immunodeficiency (SCID) mice. Passive immunization of SCID mice with anti-ganglioside G(D2) antibody resulted in significant inhibition of growth of Fc(gamma)RIIB1-positive tumors in an intracytoplasmic-dependent manner. Altogether, these data suggest that human melanoma cells express biologically active inhibitory Fc(gamma)RIIB1, which regulates their development upon direct interaction with anti-tumor antibodies. Therefore, Fc(gamma)R expression on human tumors may be one component of the efficacy of antibody-mediated therapies, and Fc(gamma)R-positive tumors could be the most sensitive candidates for such treatments.
authors.affiliation: Unité d'Immunologie Cellulaire et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM) U 255 and Université Pierre et Marie Curie Paris VI, Centre de Recherches Biomédicales des Cordeliers, Paris, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Cassard
authors.forename: Joël F G
authors.initials: JF
authors.lastname: Cohen-Solal
authors.forename: Annie
authors.initials: A
authors.lastname: Galinha
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
authors.forename: Claire
authors.initials: C
authors.lastname: Mathiot
authors.forename: Jérôme
authors.initials: J
authors.lastname: Galon
authors.forename: Thierry
authors.initials: T
authors.lastname: Dorval
authors.forename: Alain
authors.initials: A
authors.lastname: Bernheim
authors.forename: Wolf H
authors.initials: WH
authors.lastname: Fridman
authors.forename: Catherine
authors.initials: C
authors.lastname: Sautès-Fridman
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D002455:Cell Division; D006801:Humans; D007116:Immunization, Passive; D066298:In Vitro Techniques; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000556:secondary / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D017452:Receptors, IgG / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D000912:Antibodies, Neoplasm; D017452:Receptors, IgG