Cell Reports (Jun 2018)
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 Pagliara,
- Takashi 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
Affiliations
- Hanke L. Matlung
- Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Liane Babes
- Immunology Research Group, University of Calgary, Calgary, Alberta, Canada
- Xi Wen Zhao
- Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Michel van Houdt
- Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Louise W. Treffers
- Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Dieke J. van Rees
- Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Katka Franke
- Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Karin Schornagel
- Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Paul Verkuijlen
- Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Hans Janssen
- Division of Cell Biology, the Netherlands Cancer Institute, Amsterdam, the Netherlands
- Pasi Halonen
- Division of Molecular Carcinogenesis and the NKI Robotics and Screening Center, the Netherlands Cancer Institute, Amsterdam, the Netherlands
- Cor Lieftink
- Division of Molecular Carcinogenesis and the NKI Robotics and Screening Center, the Netherlands Cancer Institute, Amsterdam, the Netherlands
- Roderick L. Beijersbergen
- Division of Molecular Carcinogenesis and the NKI Robotics and Screening Center, the Netherlands Cancer Institute, Amsterdam, the Netherlands
- Jeanette H.W. Leusen
- Immunotherapy Laboratory, Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands
- Jaap J. Boelens
- U-DANCE, Laboratory for Translational Immunology, UMC Utrecht, Utrecht, the Netherlands; Department of Pediatrics, Blood and Marrow Transplantation Program, UMC Utrecht, Utrecht, the Netherlands
- Ingrid Kuhnle
- Department of Pediatrics, University Medicine Göttingen, Göttingen, Germany
- Jutte van der Werff Ten Bosch
- Department of Pediatrics, Universitair Ziekenhuis Brussel, Brussels, Belgium
- Karl Seeger
- Department of Pediatric Oncology/Hematology, Otto-Heubner-Center for Pediatric and Adolescent Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany
- Sergio Rutella
- Division of Translational Medicine, Sidra Medical and Research Center, Doha, Qatar
- Daria Pagliara
- Department of Pediatric Hematology/Oncology, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
- Takashi Matozaki
- Department of Biochemistry and Molecular Biology, Division of Molecular and Cellular Signaling, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
- Eiji Suzuki
- Department of Breast Surgery, Kyoto University Hospital, Kyoto, Japan
- Catharina Willemien Menke-van der Houven van Oordt
- Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands
- Robin van Bruggen
- Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Dirk Roos
- Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Rene A.W. van Lier
- Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Taco W. Kuijpers
- Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Emma Children’s Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands
- Paul Kubes
- Immunology Research Group, University of Calgary, Calgary, Alberta, Canada
- Timo K. van den Berg
- Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Department of Molecular Cell Biology and Immunology, VU Medical Center, Amsterdam, the Netherlands; Corresponding author
- Journal volume & issue
-
Vol. 23,
no. 13
pp. 3946 – 3959.e6
Abstract
Summary: 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. : Matlung et al. identify trogoptosis as an immune cell-mediated mechanism of cytotoxicity, demonstrating that neutrophil-mediated destruction of antibody-opsonized cancer cells occurs through a specific process that is distinct from that used by other immune cells. Keywords: antibody-dependent cellular cytotoxicity, neutrophils, CD47-SIRPα interaction, trogocytosis, trogoptosis
