| Literature DB >> 29949776 |
Hanke L Matlung1, Liane Babes2, Xi Wen Zhao1, Michel van Houdt1, Louise W Treffers1, Dieke J van Rees1, Katka Franke1, Karin Schornagel1, Paul Verkuijlen1, Hans Janssen3, Pasi Halonen4, Cor Lieftink4, Roderick L Beijersbergen4, Jeanette H W Leusen5, Jaap J Boelens6, Ingrid Kuhnle7, Jutte van der Werff Ten Bosch8, Karl Seeger9, Sergio Rutella10, Daria Pagliara11, Takashi Matozaki12, Eiji Suzuki13, Catharina Willemien Menke-van der Houven van Oordt14, Robin van Bruggen1, Dirk Roos1, Rene A W van Lier1, Taco W Kuijpers15, Paul Kubes2, Timo K van den Berg16.
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. CrownEntities:
Keywords: CD47-SIRPα interaction; antibody-dependent cellular cytotoxicity; neutrophils; trogocytosis; trogoptosis
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Year: 2018 PMID： 29949776 DOI： 10.1016/j.celrep.2018.05.082
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423