Статья

Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis

Hanke L. MatlungSanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the NetherlandsLiane BabesImmunology Research Group, University of Calgary, Calgary, Alberta, CanadaXi ZhaoSanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the NetherlandsMichel van HoudtSanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the NetherlandsLouise W. TreffersSanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the NetherlandsDieke J. van ReesSanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the NetherlandsKatka FrankeSanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the NetherlandsKarin SchornagelSanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the NetherlandsPaul VerkuijlenSanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the NetherlandsHans JanßenDivision of Cell Biology, the Netherlands Cancer Institute, Amsterdam, the NetherlandsPasi HalonenDivision of Molecular Carcinogenesis and the NKI Robotics and Screening Center, the Netherlands Cancer Institute, Amsterdam, the NetherlandsCor LieftinkDivision of Molecular Carcinogenesis and the NKI Robotics and Screening Center, the Netherlands Cancer Institute, Amsterdam, the NetherlandsRoderick L. BeijersbergenDivision of Molecular Carcinogenesis and the NKI Robotics and Screening Center, the Netherlands Cancer Institute, Amsterdam, the NetherlandsJeanette H.W. LeusenImmunotherapy Laboratory, Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, the NetherlandsJaap Jan BoelensU-DANCE, Laboratory for Translational Immunology, UMC Utrecht, Utrecht, the Netherlands; Department of Pediatrics, Blood and Marrow Transplantation Program, UMC Utrecht, Utrecht, the NetherlandsIngrid KühnleDepartment of Pediatrics, University Medicine Göttingen, Göttingen, GermanyJutte van der Werff ten BoschDepartment of Pediatrics, Universitair Ziekenhuis Brussel, Brussels, BelgiumKarl SeegerDepartment of Pediatric Oncology/Hematology, Otto-Heubner-Center for Pediatric and Adolescent Medicine, Charité-Universitätsmedizin Berlin, Berlin, GermanySergio RutellaDivision of Translational Medicine, Sidra Medical and Research Center, Doha, QatarDaria PagliaraDepartment of Pediatric Hematology/Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, ItalyTakashi MatozakiDepartment of Biochemistry and Molecular Biology, Division of Molecular and Cellular Signaling, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanEiji SuzukiDepartment of Breast Surgery, Kyoto University Hospital, Kyoto, JapanC. Willemien Menke‐van der Houven van OordtDepartment of Medical Oncology, VU University Medical Center, Amsterdam, the NetherlandsRobin van BruggenSanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the NetherlandsDirk RoosSanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the NetherlandsRené A. W. van LierSanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the NetherlandsTaco W. KuijpersUniversity of AmsterdamPaul KubesImmunology Research Group, University of Calgary, Calgary, Alberta, CanadaTimo K. van den BergSanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Department of Molecular Cell Biology and Immunology, VU Medical Center, Amsterdam, the Netherlands. Electronic address: [email protected]

2018en

ABI

Аннотация

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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Идентификаторы

DOI: 10.1016/j.celrep.2018.05.082

Цитирования и источники

Цитирований: 2Использованных источников: 0

Показатели — AkademScholar