Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis

Hanke L Matlung, Liane Babes, Xi Wen Zhao, Michel van Houdt, Louise W Treffers, Dieke J van Rees, Katka Franke, Karin Schornagel, Paul Verkuijlen, Hans Janssen, Pasi Halonen, Cor Lieftink, Roderick L Beijersbergen, Jeanette H W Leusen, Jaap J Boelens, Ingrid Kuhnle, Jutte van der Werff Ten Bosch, Karl Seeger, Sergio Rutella, Daria PagliaraTakashi Matozaki, Eiji Suzuki, Catharina Willemien Menke-van der Houven van Oordt, Robin van Bruggen, Dirk Roos, Rene A W van Lier, Taco W Kuijpers, Paul Kubes, Timo K van den Berg

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)3946-3959.e6
JournalCell Reports
Volume23
Issue number13
DOIs
Publication statusPublished - Jun 26 2018

Fingerprint

Neutrophils
Cells
Antibodies
Cytotoxicity
Neoplasms
Cell membranes
Cell Membrane
Fc Receptors
Cell death
Cell Death

Cite this

Matlung, H. L., Babes, L., Zhao, X. W., van Houdt, M., Treffers, L. W., van Rees, D. J., ... van den Berg, T. K. (2018). Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis. Cell Reports, 23(13), 3946-3959.e6. https://doi.org/10.1016/j.celrep.2018.05.082

Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis. / 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.

In: Cell Reports, Vol. 23, No. 13, 26.06.2018, p. 3946-3959.e6.

Research output: Contribution to journalArticle

Matlung, HL, Babes, L, Zhao, XW, van Houdt, M, Treffers, LW, van Rees, DJ, Franke, K, Schornagel, K, Verkuijlen, P, Janssen, H, Halonen, P, Lieftink, C, Beijersbergen, RL, Leusen, JHW, Boelens, JJ, Kuhnle, I, van der Werff Ten Bosch, J, Seeger, K, Rutella, S, Pagliara, D, Matozaki, T, Suzuki, E, Menke-van der Houven van Oordt, CW, van Bruggen, R, Roos, D, van Lier, RAW, Kuijpers, TW, Kubes, P & van den Berg, TK 2018, 'Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis', Cell Reports, vol. 23, no. 13, pp. 3946-3959.e6. https://doi.org/10.1016/j.celrep.2018.05.082
Matlung HL, Babes L, Zhao XW, van Houdt M, Treffers LW, van Rees DJ et al. Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis. Cell Reports. 2018 Jun 26;23(13):3946-3959.e6. https://doi.org/10.1016/j.celrep.2018.05.082
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. / Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis. In: Cell Reports. 2018 ; Vol. 23, No. 13. pp. 3946-3959.e6.
@article{ac530e2168304f0cac7d3f4898a6d57f,
title = "Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis",
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.",
author = "Matlung, {Hanke L} and Liane Babes and Zhao, {Xi Wen} and {van Houdt}, Michel and Treffers, {Louise W} and {van Rees}, {Dieke J} and Katka Franke and Karin Schornagel and Paul Verkuijlen and Hans Janssen and Pasi Halonen and Cor Lieftink and Beijersbergen, {Roderick L} and Leusen, {Jeanette H W} and Boelens, {Jaap J} and Ingrid Kuhnle and {van der Werff Ten Bosch}, Jutte and Karl Seeger and Sergio Rutella and Daria Pagliara and Takashi Matozaki and Eiji Suzuki and {Menke-van der Houven van Oordt}, {Catharina Willemien} and {van Bruggen}, Robin and Dirk Roos and {van Lier}, {Rene A W} and Kuijpers, {Taco W} and Paul Kubes and {van den Berg}, {Timo K}",
note = "Crown Copyright {\circledC} 2018. Published by Elsevier Inc. All rights reserved.",
year = "2018",
month = "6",
day = "26",
doi = "10.1016/j.celrep.2018.05.082",
language = "English",
volume = "23",
pages = "3946--3959.e6",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "13",

}

TY - JOUR

T1 - Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis

AU - Matlung, Hanke L

AU - Babes, Liane

AU - Zhao, Xi Wen

AU - van Houdt, Michel

AU - Treffers, Louise W

AU - van Rees, Dieke J

AU - Franke, Katka

AU - Schornagel, Karin

AU - Verkuijlen, Paul

AU - Janssen, Hans

AU - Halonen, Pasi

AU - Lieftink, Cor

AU - Beijersbergen, Roderick L

AU - Leusen, Jeanette H W

AU - Boelens, Jaap J

AU - Kuhnle, Ingrid

AU - van der Werff Ten Bosch, Jutte

AU - Seeger, Karl

AU - Rutella, Sergio

AU - Pagliara, Daria

AU - Matozaki, Takashi

AU - Suzuki, Eiji

AU - Menke-van der Houven van Oordt, Catharina Willemien

AU - van Bruggen, Robin

AU - Roos, Dirk

AU - van Lier, Rene A W

AU - Kuijpers, Taco W

AU - Kubes, Paul

AU - van den Berg, Timo K

N1 - Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

PY - 2018/6/26

Y1 - 2018/6/26

N2 - 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.

AB - 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.

U2 - 10.1016/j.celrep.2018.05.082

DO - 10.1016/j.celrep.2018.05.082

M3 - Article

C2 - 29949776

VL - 23

SP - 3946-3959.e6

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 13

ER -