Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis

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-opsoni...

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Veröffentlicht in:Cell reports (Cambridge) Jg. 23; H. 13; S. 3946 - 3959.e6
Hauptverfasser: 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
Sprache:Englisch
Veröffentlicht: United States Elsevier Inc 26.06.2018
Elsevier
Schlagworte:
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
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2018.05.082