title: Enhanced FcαRI-mediated neutrophil migration towards tumour colonies in the presence of endothelial cells.
abstract: Neutrophils potently kill tumour cells in the presence of anti-tumour antibodies in vitro. However, for in vivo targeting, the neutrophils need to extravasate from the circulation by passing through endothelial barriers. To study neutrophil migration in the presence of endothelial cells in vitro, we established a three-dimensional collagen culture in which SK-BR-3 tumour colonies were grown in the presence or absence of an endothelial barrier. We demonstrated that - in contrast to targeting FcγR on neutrophils with mAbs - targeting the immunoglobulin A Fc receptor (FcαRI) instead triggered neutrophil migration and degranulation leading to tumour destruction, which coincided with release of the pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α. Interestingly, neutrophil migration was enhanced in the presence of endothelial cells, which coincided with production of significant levels of the neutrophil chemokine IL-8. This supports the idea that stimulation of neutrophil FcαRI, but not FcγR, initiates cross-talk between neutrophils and endothelial cells, leading to enhanced neutrophil migration towards tumour colonies and subsequent tumour killing.
authors.affiliation: Immunotherapy Laboratory, Department of Immunology, UMC, Utrecht, The Netherlands.
authors.forename: Marielle A
authors.initials: MA
authors.lastname: Otten
authors.forename: Jantine E
authors.initials: JE
authors.lastname: Bakema
authors.forename: Cornelis W
authors.initials: CW
authors.lastname: Tuk
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Glennie
authors.forename: Alison L
authors.initials: AL
authors.lastname: Tutt
authors.forename: Robert H J
authors.initials: RH
authors.lastname: Beelen
authors.forename: Jan G J
authors.initials: JG
authors.lastname: van de Winkel
authors.forename: Marjolein
authors.initials: M
authors.lastname: van Egmond
mesh_terms: D015703:Antigens, CD / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D002450:Cell Communication / Q000276:immunology; D045744:Cell Line, Tumor; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000032:analysis / Q000276:immunology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology
chemical_list: D015703:Antigens, CD; C036832:Fc(alpha) receptor; D053583:Interleukin-1beta; D011961:Receptors, Fc; D014409:Tumor Necrosis Factor-alpha