Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis

作者：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; Beijer**ergen Roderick L; Leusen Jeanette H W; Boelens Jaap J; Kuhnle Ingrid; Ten Bosch Jutte van der Werff; Seeger Karl; Rutella Sergio; Pagliara Daria; Matozaki Takashi; Suzuki Eiji; Willemien Catharina; van Oordt Menke van der Houven; van Bruggen Robin; Roos Dirk

来源：Cell Reports, 2018, 23(13): 3946-+.

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-SIRP alpha 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-SIRPcx interactions.

• 出版日期2018-6-26