RESUMEN
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.
Asunto(s)
Melanoma/inmunología , Receptores de IgG/metabolismo , Animales , Anticuerpos Antineoplásicos/sangre , División Celular , Humanos , Inmunización Pasiva , Técnicas In Vitro , Melanoma/patología , Melanoma/secundario , Melanoma/terapia , Ratones , Ratones Desnudos , Ratones SCID , Trasplante de Neoplasias , Receptores de IgG/química , Receptores de IgG/genética , Transfección , Trasplante Heterólogo , Células Tumorales CultivadasRESUMEN
N-glycans of human Fcgamma receptor III (FcgammaR III) are believed to be involved in the interaction with complement receptor type 3 (CR3) (Sehgal et al. [1993] J. Immunol., 150, 4571-4580). Recombinant human soluble FcgammaRIII (rhsFcgammaRIII), which is produced in baby hamster kidney (BHK) cells, has been shown to interact with CR3 in a manner similar to native FcgammaRIII. We elucidated the N-glycosylation profiles of rhsFcgammaRIII by the 3D high-performance liquid chromatography mapping technique. It was revealed that the N-glycans of rhsFcgammaRIII are much more divergent (consisting of 20 neutral, 7 monosialyl, 4 disialyl, 5 trisialyl, and 1 tetrasialyl oligosaccharides) than those previously determined for BHK-expressed mouse sFcgammaRII, notwithstanding close structural similarity of polypeptide chains between the two sFcgammaRs. Particularly, high-mannose type oligosaccharides are specifically expressed on rhsFcgammaRIII.