10.3389/fimmu.2018.03124.s001
Louise W. Treffers
Louise W.
Treffers
Michel van Houdt
Michel
van Houdt
Christine W. Bruggeman
Christine W.
Bruggeman
Marieke H. Heineke
Marieke H.
Heineke
Xi Wen Zhao
Xi Wen
Zhao
Joris van der Heijden
Joris
van der Heijden
Sietse Q. Nagelkerke
Sietse
Q. Nagelkerke
Paul J. J. H. Verkuijlen
Paul J. J. H.
Verkuijlen
Judy Geissler
Judy
Geissler
Suzanne Lissenberg-Thunnissen
Suzanne
Lissenberg-Thunnissen
Thomas Valerius
Thomas
Valerius
Matthias Peipp
Matthias
Peipp
Katka Franke
Katka
Franke
Robin van Bruggen
Robin
van Bruggen
Taco W. Kuijpers
Taco
W. Kuijpers
Marjolein van Egmond
Marjolein
van Egmond
Gestur Vidarsson
Gestur
Vidarsson
Hanke L. Matlung
Hanke
L. Matlung
Timo K. van den Berg
Timo
K. van den Berg
Data_Sheet_1_FcγRIIIb Restricts Antibody-Dependent Destruction of Cancer Cells by Human Neutrophils.PDF
Frontiers
2019
FcγRIIIb
neutrophil
ADCC
cancer
granulocyte
Fc-receptor
CNV
glycoengineering
2019-01-30 04:10:41
Dataset
https://frontiersin.figshare.com/articles/dataset/Data_Sheet_1_Fc_RIIIb_Restricts_Antibody-Dependent_Destruction_of_Cancer_Cells_by_Human_Neutrophils_PDF/7647728
<p>The function of the low-affinity IgG-receptor FcγRIIIb (CD16b), which is uniquely and abundantly expressed on human granulocytes, is not clear. Unlike the other Fcγ receptors (FcγR), it is a glycophosphatidyl inositol (GPI) -anchored molecule and does not have intracellular signaling motifs. Nevertheless, FcγRIIIb can cooperate with other FcγR to promote phagocytosis of antibody-opsonized microbes by human neutrophils. Here we have investigated the role of FcγRIIIb during antibody-dependent cellular cytotoxicity (ADCC) by neutrophils toward solid cancer cells coated with either trastuzumab (anti-HER2) or cetuximab (anti-EGFR). Inhibiting FcγRIIIb using CD16-F(ab')<sub>2</sub> blocking antibodies resulted in substantially enhanced ADCC. ADCC was completely dependent on FcγRIIa (CD32a) and the enhanced ADCC seen after FcγRIIIb blockade therefore suggested that FcγRIIIb was competing with FcγRIIa for IgG on the opsonized target cells. Interestingly, the function of neutrophil FcγRIIIb as a decoy receptor was further supported by using neutrophils from individuals with different gene copy numbers of FCGR3B causing different levels of surface FcγRIIIb expression. Individuals with one copy of FCGR3B showed higher levels of ADCC compared to those with two or more copies. Finally, we show that therapeutic antibodies intended to improve FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC due to the lack of fucosylation on the N-linked glycan at position N297 of the IgG<sub>1</sub> heavy chain Fc-region, show decreased ADCC as compared to regularly fucosylated antibodies. Together, these data confirm FcγRIIIb as a negative regulator of neutrophil ADCC toward tumor cells and a potential target for enhancing tumor cell destruction by neutrophils.</p>