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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorvan Rees, Dieke
dc.contributor.authorBouti, Panagiota
dc.contributor.authorKlein, Bart
dc.contributor.authorVerkuijlen, Paul JH
dc.contributor.authorvan Houdt, Michel
dc.contributor.authorSchornagel, Karin
dc.contributor.authorSaura Manich, Cristina
dc.date.accessioned2022-09-09T12:27:38Z
dc.date.available2022-09-09T12:27:38Z
dc.date.issued2022-06
dc.identifier.citationvan Rees DJ, Bouti P, Klein B, Verkuijlen PJH, van Houdt M, Schornagel K, et al. Cancer cells resist antibody-mediated destruction by neutrophils through activation of the exocyst complex. J Immunother Cancer. 2022 Jun;10(6):e004820.
dc.identifier.issn2051-1426
dc.identifier.urihttp://hdl.handle.net/11351/8113
dc.descriptionCytotoxicity; Immunity; Immunotherapy
dc.description.abstractBackground Neutrophils kill antibody-opsonized tumor cells using trogocytosis, a unique mechanism of destruction of the target plasma. This previously unknown cytotoxic process of neutrophils is dependent on antibody opsonization, Fcγ receptors and CD11b/CD18 integrins. Here, we demonstrate that tumor cells can escape neutrophil-mediated cytotoxicity by calcium (Ca2+)-dependent and exocyst complex-dependent plasma membrane repair. Methods We knocked down EXOC7 or EXOC4, two exocyst components, to evaluate their involvement in tumor cell membrane repair after neutrophil-induced trogocytosis. We used live cell microscopy and flow cytometry for visualization of the host and tumor cell interaction and tumor cell membrane repair. Last, we reported the mRNA levels of exocyst in breast cancer tumors in correlation to the response in trastuzumab-treated patients. Results We found that tumor cells can evade neutrophil antibody-dependent cellular cytotoxicity (ADCC) by Ca2+-dependent cell membrane repair, a process induced upon neutrophil trogocytosis. Absence of exocyst components EXOC7 or EXOC4 rendered tumor cells vulnerable to neutrophil-mediated ADCC (but not natural killer cell-mediated killing), while neutrophil trogocytosis remained unaltered. Finally, mRNA levels of exocyst components in trastuzumab-treated patients were inversely correlated to complete response to therapy. Conclusions Our results support that neutrophil attack towards antibody-opsonized cancer cells by trogocytosis induces an active repair process by the exocyst complex in vitro. Our findings provide insight to the possible contribution of neutrophils in current antibody therapies and the tolerance mechanism of tumor cells and support further studies for potential use of the exocyst components as clinical biomarkers.
dc.language.isoeng
dc.publisherBMJ
dc.relation.ispartofseriesJournal for ImmunoTherapy of Cancer;10(6)
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.sourceScientia
dc.subjectCàncer - Tractament
dc.subjectImmunoglobulines - Ús terapèutic
dc.subjectCitotoxicitat per mediació cel·lular
dc.subject.meshAntibody-Dependent Cell Cytotoxicity
dc.subject.meshNeutrophils
dc.subject.meshNeoplasms
dc.subject.mesh/therapy
dc.titleCancer cells resist antibody-mediated destruction by neutrophils through activation of the exocyst complex
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1136/jitc-2022-004820
dc.subject.decscitotoxicidad celular dependiente de anticuerpos
dc.subject.decsneutrófilos
dc.subject.decsneoplasias
dc.subject.decs/terapia
dc.relation.publishversionhttp://dx.doi.org/10.1136/jitc-2022-004820
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[van Rees DJ, Bouti P, Klein B, Verkuijlen PJH, van Houdt M, Schornagel K] Department of Molecular Hematology, Sanquin Research, Amsterdam, The Netherlands. [Saura C] SOLTI Innovative Breast Cancer Research, Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain
dc.identifier.pmid35728876
dc.identifier.wos000815215400006
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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