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 Pagliara; Takashi 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

doi:10.1016/j.celrep.2018.05.082

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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-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 language	English
Pages (from-to)	3946-3959.e6
Journal	Cell Reports
Volume	23
Issue number	13
DOIs	https://doi.org/10.1016/j.celrep.2018.05.082 https://doi.org/10.1016/j.celrep.2018.05.082
Publication status	Published - 26 Jun 2018

Keywords

Animals
Antibodies, Monoclonal/therapeutic use
Antibody-Dependent Cell Cytotoxicity
CD11b Antigen/metabolism
CD18 Antigens/metabolism
CD47 Antigen/metabolism
Cell Line, Tumor
Female
Humans
Male
Melanoma, Experimental/metabolism
Mice
Mice, Inbred C57BL
Neoplasms/drug therapy
Neutrophils/immunology
Receptors, IgG/metabolism
Receptors, Immunologic/genetics
Transplantation, Homologous

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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., ... 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, https://doi.org/10.1016/j.celrep.2018.05.082

@article{0ba45acb2d9f4a939d9811c64bc7091e,

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.",

keywords = "Animals, Antibodies, Monoclonal/therapeutic use, Antibody-Dependent Cell Cytotoxicity, CD11b Antigen/metabolism, CD18 Antigens/metabolism, CD47 Antigen/metabolism, Cell Line, Tumor, Female, Humans, Male, Melanoma, Experimental/metabolism, Mice, Mice, Inbred C57BL, Neoplasms/drug therapy, Neutrophils/immunology, Receptors, IgG/metabolism, Receptors, Immunologic/genetics, Transplantation, Homologous",

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 = "Funding Information: We are grateful to Dr. {\"O}zden Sanal (Hacettepe University, Ankara, Turkey) for providing patient material; to Ben Morris, Erik Mul, Anton Tool, and Edith van de Vijver for their help with the experiments and/or their analysis; and to Georg Kraal, S{\o}ren Moestrup, Sjaak Neefjes, and Arnoud Sonnenberg for useful discussions and for critically reading the manuscript. We also gratefully acknowledge the contribution of Joost Bakker from SciComVisuals for graphics, including the Graphical Abstract. This research was funded in part by the Dutch Cancer Society (grant no. 10300) and the Landsteiner Research Foundation (grant no. 1223). Funding Information: We are grateful to Dr. {\"O}zden Sanal (Hacettepe University, Ankara, Turkey) for providing patient material; to Ben Morris, Erik Mul, Anton Tool, and Edith van de Vijver for their help with the experiments and/or their analysis; and to Georg Kraal, S{\o}ren Moestrup, Sjaak Neefjes, and Arnoud Sonnenberg for useful discussions and for critically reading the manuscript. We also gratefully acknowledge the contribution of Joost Bakker from SciComVisuals for graphics, including the Graphical Abstract. This research was funded in part by the Dutch Cancer Society (grant no. 10300 ) and the Landsteiner Research Foundation (grant no. 1223 ). Publisher Copyright: {\textcopyright} 2018",

year = "2018",

month = jun,

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",

}

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, https://doi.org/10.1016/j.celrep.2018.05.082

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 - Funding Information: We are grateful to Dr. Özden Sanal (Hacettepe University, Ankara, Turkey) for providing patient material; to Ben Morris, Erik Mul, Anton Tool, and Edith van de Vijver for their help with the experiments and/or their analysis; and to Georg Kraal, Søren Moestrup, Sjaak Neefjes, and Arnoud Sonnenberg for useful discussions and for critically reading the manuscript. We also gratefully acknowledge the contribution of Joost Bakker from SciComVisuals for graphics, including the Graphical Abstract. This research was funded in part by the Dutch Cancer Society (grant no. 10300) and the Landsteiner Research Foundation (grant no. 1223). Funding Information: We are grateful to Dr. Özden Sanal (Hacettepe University, Ankara, Turkey) for providing patient material; to Ben Morris, Erik Mul, Anton Tool, and Edith van de Vijver for their help with the experiments and/or their analysis; and to Georg Kraal, Søren Moestrup, Sjaak Neefjes, and Arnoud Sonnenberg for useful discussions and for critically reading the manuscript. We also gratefully acknowledge the contribution of Joost Bakker from SciComVisuals for graphics, including the Graphical Abstract. This research was funded in part by the Dutch Cancer Society (grant no. 10300 ) and the Landsteiner Research Foundation (grant no. 1223 ). Publisher Copyright: © 2018

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.

KW - Animals

KW - Antibodies, Monoclonal/therapeutic use

KW - Antibody-Dependent Cell Cytotoxicity

KW - CD11b Antigen/metabolism

KW - CD18 Antigens/metabolism

KW - CD47 Antigen/metabolism

KW - Cell Line, Tumor

KW - Female

KW - Humans

KW - Male

KW - Melanoma, Experimental/metabolism

KW - Mice

KW - Mice, Inbred C57BL

KW - Neoplasms/drug therapy

KW - Neutrophils/immunology

KW - Receptors, IgG/metabolism

KW - Receptors, Immunologic/genetics

KW - Transplantation, Homologous

UR - http://www.scopus.com/inward/record.url?scp=85048859204&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2018.05.082

DO - 10.1016/j.celrep.2018.05.082

M3 - Article

C2 - 29949776

AN - SCOPUS:85048859204

SN - 2211-1247

VL - 23

SP - 3946-3959.e6

JO - Cell Reports

JF - Cell Reports

IS - 13

ER -

Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis

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