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 journalArticleAcademicpeer-review

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 - 26 Jun 2018

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