Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis
Matlung, Hanke L.; Babes, Liane; Zhao, Xi Wen; van Houdt, Michel; Treffers, Louise W.; van Rees, Dieke J.; Franke, Katka; Schornagel, Karin; Verkuijlen, Paul; Janssen, Hans; Halonen, Pasi; Lieftink, Cor; Beijersbergen, Roderick L.; Leusen, Jeanette H.W.; Boelens, Jaap J.; Kuhnle, Ingrid; van der Werff Ten Bosch, Jutte; Seeger, Karl; Rutella, Sergio; Pagliara, Daria; Matozaki, Takashi; Suzuki, Eiji; Menke-van der Houven van Oordt, Catharina Willemien; van Bruggen, Robin; Roos, Dirk; van Lier, Rene A.W.; Kuijpers, Taco W.; Kubes, Paul; van den Berg, Timo K.
(2018) Cell Reports, volume 23, issue 13, pp. 3946 - 3959.e6
(Article)
Abstract
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
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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.
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Keywords: Animals, Antibodies, Monoclonal/therapeutic use, Antibody-Dependent Cell Cytotoxicity, CD11b Antigen/metabolism, CD18 Antigens/metabolism, CD47 Antigen/metabolism, Cell Line, Tumor, Female, Humans, Male, Melanoma, Experimental/metabolism, Mice, Mice, Inbred C57BL, Neoplasms/drug therapy, Neutrophils/immunology, Receptors, IgG/metabolism, Receptors, Immunologic/genetics, Transplantation, Homologous, General Biochemistry,Genetics and Molecular Biology, Journal Article, Research Support, Non-U.S. Gov't
ISSN: 2211-1247
Publisher: Cell Press
Note: Funding Information: We are grateful to Dr. Özden Sanal (Hacettepe University, Ankara, Turkey) for providing patient material; to Ben Morris, Erik Mul, Anton Tool, and Edith van de Vijver for their help with the experiments and/or their analysis; and to Georg Kraal, Søren Moestrup, Sjaak Neefjes, and Arnoud Sonnenberg for useful discussions and for critically reading the manuscript. We also gratefully acknowledge the contribution of Joost Bakker from SciComVisuals for graphics, including the Graphical Abstract. This research was funded in part by the Dutch Cancer Society (grant no. 10300) and the Landsteiner Research Foundation (grant no. 1223). Funding Information: We are grateful to Dr. Özden Sanal (Hacettepe University, Ankara, Turkey) for providing patient material; to Ben Morris, Erik Mul, Anton Tool, and Edith van de Vijver for their help with the experiments and/or their analysis; and to Georg Kraal, Søren Moestrup, Sjaak Neefjes, and Arnoud Sonnenberg for useful discussions and for critically reading the manuscript. We also gratefully acknowledge the contribution of Joost Bakker from SciComVisuals for graphics, including the Graphical Abstract. This research was funded in part by the Dutch Cancer Society (grant no. 10300 ) and the Landsteiner Research Foundation (grant no. 1223 ). Publisher Copyright: © 2018
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