Immature neutrophils mediate tumor cell killing via IgA but not IgG Fc receptors.
Antitumor Abs are promising therapeutics for cancer. Currently, most Ab-based therapies focus on IgG Ab, which interact with IgG FcR (FcgammaR) on effector cells. In this study, we examined human and mouse neutrophil-mediated tumor cell lysis via targeting the IgA FcR, FcalphaRI (CD89), in more detail. FcalphaRI was the most effective FcR in triggering tumor cell killing, and initiated enhanced migration of neutrophils into tumor colonies. Importantly, immature neutrophils that are mobilized from the bone marrow upon G-CSF treatment efficiently triggered tumor cell lysis via FcalphaRI, but proved incapable of initiating tumor cell killing via FcgammaR. This may provide a rationale for the disappointing results observed in some earlier clinical trials in which patients were treated with G-CSF and antitumor Ab-targeting FcgammaR.
Otten
Marielle A
MA
Immunotherapy Laboratory, Department of Immunology, University Medical Center Utrecht, The Netherlands.
Rudolph
Esther
E
Dechant
Michael
M
Tuk
Cornelis W
CW
Reijmers
Rogier M
RM
Beelen
Robert H J
RH
van de Winkel
Jan G J
JG
van Egmond
Marjolein
M
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000235:genetics / Q000276:immunology*; D015703:Antigens, CD / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D011961:Receptors, Fc / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000502:physiology*; D017452:Receptors, IgG / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014741:Video Recording
D015703:Antigens, CD; C036832:Fc(alpha) receptor; D011961:Receptors, Fc; D017452:Receptors, IgG; D016179:Granulocyte Colony-Stimulating Factor