Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 42, Issue 7, Pages 1815-1821Publisher
WILEY
DOI: 10.1002/eji.201141982
Keywords
Bispecific antibody; Chemotaxis immunotherapy; HUVEC; IgA
Categories
Funding
- Dutch Cancer Society [UU2001-2431]
- Stichting VUmc Cancer Center Amsterdam
- Netherlands Organization for Scientific Research [VENI 916.36.079, VIDI 016.086.320]
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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 Fc?R on neutrophils with mAbs targeting the immunoglobulin A Fc receptor (FcaRI) instead triggered neutrophil migration and degranulation leading to tumour destruction, which coincided with release of the pro-inflammatory cytokines interleukin (IL)-1 beta and tumour necrosis factor (TNF)-a. 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 FcaRI, but not Fc?R, initiates cross-talk between neutrophils and endothelial cells, leading to enhanced neutrophil migration towards tumour colonies and subsequent tumour killing.
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