Neutrophils kill antibody-opsonized cancer cells by trogoptosis

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. ORCID: 0000-0003-1970-7375, 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. and Van den Berg, T.K., 2018. Neutrophils kill antibody-opsonized cancer cells by trogoptosis. Cell Reports, 23 (13), pp. 3946-3959. ISSN 2211-1247

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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-SIRPa 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-SIRPa interactions.

Item Type: Journal article
Publication Title: Cell Reports
Creators: 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. and Van den Berg, T.K.
Publisher: Elsevier
Date: 26 June 2018
Volume: 23
Number: 13
ISSN: 2211-1247
Identifiers:
NumberType
10.1016/j.celrep.2018.05.082DOI
Divisions: Schools > School of Science and Technology
Depositing User: Linda Sullivan
Date Added: 28 Jun 2018 13:37
Last Modified: 02 Aug 2018 14:09
URI: http://irep.ntu.ac.uk/id/eprint/33943

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