Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis
Publication date
2018-06-26
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
Editors
Advisors
Supervisors
Document Type
Article
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cc_by_nc_nd
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.
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
Citation
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, Pagliara, D, Matozaki, T, Suzuki, E, Menke-van der Houven van Oordt, C W, van Bruggen, R, Roos, D, van Lier, R A W, Kuijpers, T W, Kubes, P & van den Berg, T K 2018, 'Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis', Cell Reports, vol. 23, no. 13, pp. 3946-3959.e6. https://doi.org/10.1016/j.celrep.2018.05.082, https://doi.org/10.1016/j.celrep.2018.05.082