Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis

Hanke L Matlung, Liane Babes, Xi Wen Zhao, Michel van Houdt, Louise W Treffers, Dieke J van Rees, Katka Franke, Karin Schornagel, Paul Verkuijlen, Hans Janssen, Pasi Halonen, Cor Lieftink, Roderick L Beijersbergen, Jeanette H W Leusen, Jaap J Boelens, Ingrid Kuhnle, Jutte van der Werff Ten Bosch, Karl Seeger, Sergio Rutella, Daria PagliaraTakashi Matozaki, Eiji Suzuki, Catharina Willemien Menke-van der Houven van Oordt, Robin van Bruggen, Dirk Roos, Rene A W van Lier, Taco W Kuijpers, Paul Kubes, Timo K van den Berg

Research output: Contribution to journalArticle

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 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.

Original languageEnglish
Pages (from-to)3946-3959.e6
JournalCell Reports
Volume23
Issue number13
DOIs
Publication statusPublished - Jun 26 2018

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    Matlung, H. L., Babes, L., Zhao, X. W., van Houdt, M., Treffers, L. W., van Rees, D. J., Franke, K., Schornagel, K., Verkuijlen, P., Janssen, H., Halonen, P., Lieftink, C., Beijersbergen, R. L., Leusen, J. H. W., Boelens, J. J., Kuhnle, I., van der Werff Ten Bosch, J., Seeger, K., Rutella, S., ... van den Berg, T. K. (2018). Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis. Cell Reports, 23(13), 3946-3959.e6. https://doi.org/10.1016/j.celrep.2018.05.082