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Immature Neutrophils Mediate Tumor Cell Killing via IgA but Not IgG Fc Receptors¹

Marielle A. Otten^*,, Esther Rudolph^*,, Michael Dechant^¶, Cornelis W. Tuk, Rogier M. Reijmers, Robert H. J. Beelen, Jan G. J. van de Winkel^*, and Marjolein van Egmond^2,,

^* Immunotherapy Laboratory, Department of Immunology, University Medical Center Utrecht, and Genmab, Utrecht, The Netherlands; Departments of Molecular Cell Biology and Immunology and Surgical Oncology, VU University Medical Center, Amsterdam, The Netherlands; and ^¶ Division of Nephrology, University Hospital of Schleswig-Holstein, Kiel, Germany

Antitumor Abs are promising therapeutics for cancer. Currently, most Ab-based therapies focus on IgG Ab, which interact with IgG FcR (FcR) on effector cells. In this study, we examined human and mouse neutrophil-mediated tumor cell lysis via targeting the IgA FcR, FcRI (CD89), in more detail. FcRI 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 FcRI, but proved incapable of initiating tumor cell killing via FcR. 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 FcR.

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