Enhancement of polymorphonuclear cell-mediated tumor cell killing on simultaneous engagement of fcgammaRI (CD64) and fcalphaRI (CD89).
Antibodies can efficiently induce antitumor responses via recruitment of Fc receptor-bearing cytotoxic cells. Polymorphonuclear (PMN) cells represent attractive effector cells for antibody-directed immunotherapy. This, because activated PMN cells coexpress the class I receptors for IgG (FcgammaRI, CD64) and IgA (FcalphaRI, CD89), which are potent cytotoxic trigger molecules. Both receptors, however, require the FcR gamma chain for signaling. In this study, we show that FcgammaRI and FcalphaRI can trigger function independently of one another and do not cross-compete for the FcR gamma chain. FcalphaRI proved more efficient in initiating early signaling events and effector functions, such as redirected tumor cell killing and generation of superoxide. In addition, simultaneous engagement of FcgammaRI and FcalphaRI resulted in enhanced tumor cell lysis. These data support the development of concepts in which both FcgammaRI and FcalphaRI on PMN cells are targeted for tumor therapy.
van Egmond
M
M
Department of Cell Biology/Immunology, Vrije Universiteit, Amsterdam, the Netherlands.
van Spriel
A B
AB
Vermeulen
H
H
Huls
G
G
van Garderen
E
E
van de Winkel
J G
JG
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D009101:Multiple Myeloma / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D011961:Receptors, Fc / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D017452:Receptors, IgG / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D015703:Antigens, CD; C036832:Fc(alpha) receptor; D011961:Receptors, Fc; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor