[PDF][PDF] Neutrophils kill antibody-opsonized cancer cells by trogoptosis

HL Matlung, L Babes, XW Zhao, M van Houdt… - Cell reports, 2018 - cell.com
HL Matlung, L Babes, XW Zhao, M van Houdt, LW Treffers, DJ van Rees, K Franke…
Cell reports, 2018cell.com
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 …
Summary
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.
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