Cancers (Nov 2020)

IgE Activates Monocytes from Cancer Patients to Acquire a Pro-Inflammatory Phenotype

  • Mano Nakamura,
  • Elmira Amiri Souri,
  • Gabriel Osborn,
  • Roman Laddach,
  • Jitesh Chauhan,
  • Chara Stavraka,
  • Sara Lombardi,
  • Anna Black,
  • Atousa Khiabany,
  • Duaa O. Khair,
  • Mariangela Figini,
  • Anna Winship,
  • Sharmistha Ghosh,
  • Ana Montes,
  • James F. Spicer,
  • Heather J. Bax,
  • Debra H. Josephs,
  • Katie E. Lacy,
  • Sophia Tsoka,
  • Sophia N. Karagiannis

DOI
https://doi.org/10.3390/cancers12113376
Journal volume & issue
Vol. 12, no. 11
p. 3376

Abstract

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IgE contributes to host-protective functions in parasitic and bacterial infections, often by monocyte and macrophage recruitment. We previously reported that monocytes contribute to tumour antigen-specific IgE-mediated tumour growth restriction in rodent models. Here, we investigate the impact of IgE stimulation on monocyte response, cellular signalling, secretory and tumour killing functions. IgE cross-linking on human monocytes with polyclonal antibodies to mimic formation of immune complexes induced upregulation of co-stimulatory (CD40, CD80, CD86), and reduced expression of regulatory (CD163, CD206, MerTK) monocyte markers. Cross-linking and tumour antigen-specific IgE antibody-dependent cellular cytotoxicity (ADCC) of cancer cells by cancer patient-derived monocytes triggered release of pro-inflammatory mediators (TNFα, MCP-1, IL-10, CXCL-10, IL-1β, IL-6, IL-23). High intratumoural gene expression of these mediators was associated with favourable five-year overall survival in ovarian cancer. IgE cross-linking of trimeric FcεRI on monocytes stimulated the phosphorylation of intracellular protein kinases widely reported to be downstream of mast cell and basophil tetrameric FcεRI signalling. These included recently-identified FcεRI pathway kinases Fgr, STAT5, Yes and Lck, which we now associate with monocytes. Overall, anti-tumour IgE can potentiate pro-inflammatory signals, and prime tumour cell killing by human monocytes. These findings will inform the development of IgE monoclonal antibody therapies for cancer.

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