TY - JOUR
T1 - Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis
AU - Matlung, Hanke L
AU - Babes, Liane
AU - Zhao, Xi Wen
AU - van Houdt, Michel
AU - Treffers, Louise W
AU - van Rees, Dieke J
AU - Franke, Katka
AU - Schornagel, Karin
AU - Verkuijlen, Paul
AU - Janssen, Hans
AU - Halonen, Pasi
AU - Lieftink, Cor
AU - Beijersbergen, Roderick L
AU - Leusen, Jeanette H W
AU - Boelens, Jaap J
AU - Kuhnle, Ingrid
AU - van der Werff Ten Bosch, Jutte
AU - Seeger, Karl
AU - Rutella, Sergio
AU - Pagliara, Daria
AU - Matozaki, Takashi
AU - Suzuki, Eiji
AU - Menke-van der Houven van Oordt, Catharina Willemien
AU - van Bruggen, Robin
AU - Roos, Dirk
AU - van Lier, Rene A W
AU - Kuijpers, Taco W
AU - Kubes, Paul
AU - van den Berg, Timo K
N1 - Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.
PY - 2018/6/26
Y1 - 2018/6/26
N2 - Destruction of cancer cells by therapeutic antibodies occurs, at least in part, through antibody-dependent cellular cytotoxicity (ADCC), and this can be mediated by various Fc-receptor-expressing immune cells, including neutrophils. However, the mechanism(s) by which neutrophils kill antibody-opsonized cancer cells has not been established. Here, we demonstrate that neutrophils can exert a mode of destruction of cancer cells, which involves antibody-mediated trogocytosis by neutrophils. Intimately associated with this is an active mechanical disruption of the cancer cell plasma membrane, leading to a lytic (i.e., necrotic) type of cancer cell death. Furthermore, this mode of destruction of antibody-opsonized cancer cells by neutrophils is potentiated by CD47-SIRPα checkpoint blockade. Collectively, these findings show that neutrophil ADCC toward cancer cells occurs by a mechanism of cytotoxicity called trogoptosis, which can be further improved by targeting CD47-SIRPα interactions.
AB - Destruction of cancer cells by therapeutic antibodies occurs, at least in part, through antibody-dependent cellular cytotoxicity (ADCC), and this can be mediated by various Fc-receptor-expressing immune cells, including neutrophils. However, the mechanism(s) by which neutrophils kill antibody-opsonized cancer cells has not been established. Here, we demonstrate that neutrophils can exert a mode of destruction of cancer cells, which involves antibody-mediated trogocytosis by neutrophils. Intimately associated with this is an active mechanical disruption of the cancer cell plasma membrane, leading to a lytic (i.e., necrotic) type of cancer cell death. Furthermore, this mode of destruction of antibody-opsonized cancer cells by neutrophils is potentiated by CD47-SIRPα checkpoint blockade. Collectively, these findings show that neutrophil ADCC toward cancer cells occurs by a mechanism of cytotoxicity called trogoptosis, which can be further improved by targeting CD47-SIRPα interactions.
U2 - 10.1016/j.celrep.2018.05.082
DO - 10.1016/j.celrep.2018.05.082
M3 - Article
C2 - 29949776
VL - 23
SP - 3946-3959.e6
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 13
ER -