Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis

• Published in: Cell reports (Cambridge) Vol. 23; no. 13; pp. 3946 - 3959.e6
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.06.2018; Elsevier
• Subjects: Animals; Antibodies, Monoclonal - therapeutic use; Antibody-Dependent Cell Cytotoxicity; antibody-dependent cellular cytotoxicity; CD11b Antigen - metabolism; CD18 Antigens - metabolism; CD47 Antigen - metabolism; CD47-SIRPα interaction; Cell Line, Tumor; Female; Humans; Male; Melanoma, Experimental - metabolism; Melanoma, Experimental - pathology; Mice; Mice, Inbred C57BL; Neoplasms - drug therapy; Neoplasms - immunology; Neoplasms - pathology; neutrophils; Neutrophils - immunology; Receptors, IgG - metabolism; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Transplantation, Homologous; trogocytosis; trogoptosis; trogocytosis; trogoptosis; antibody-dependent cellular cytotoxicity; CD47-SIRPα interaction; neutrophils
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2018.05.082

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. [Display omitted] •Neutrophils kill antibody-opsonized cancer cells by a process called trogoptosis•Cancer cell plasma membrane ingestion by neutrophils is instrumental in trogoptosis•Trogoptosis by neutrophils is further enhanced by CD47-SIRPα checkpoint inhibition 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.