Antitumor IgE adjuvanticity: Key role of FcεRI

Elisa A. Nigro, Anna T. Brini, Elisa Soprana, Alessandro Ambrosi, David Dombrowicz, Antonio G. Siccardi, Luca Vangelista

Research output: Contribution to journalArticlepeer-review

Abstract

Working with C57BL/6 mouse tumor models, we had previously demonstrated that vaccination with IgE-coated tumor cells can protect against tumor challenge, an observation that supports the involvement of IgE in antitumor immunity. The adjuvant effect of IgE was shown to result from eosinophil-dependent priming of the T cell-mediated adaptive immune response. The protective effect is likely to be mediated by the interaction of tumor cell-bound IgE with receptors, which then trigger the release of mediators, recruitment of effector cells, cell killing and tumor Ag cross-priming. It was therefore of utmost importance to demonstrate the strict dependence of the protective effect on IgE receptor activation. First, the protective effect of IgE was confirmed in a BALB/c tumor model, in which IgE-loaded modified VV Ankara-infected tumor cells proved to be an effective cellular vaccine. However, the protective effect was lost in FcεRIα-/- (but not in CD23-/-) knockout mice, showing the IgE-FcεRI interaction to be essential. Moreover, human IgE (not effective in BALB/c mice) had a protective effect in the humanized knockin mouse (FcεRIα-/- hFcεRIα+). This finding suggests that the adjuvant effect of IgE could be exploited for human therapeutics.

Original languageEnglish
Pages (from-to)4530-4536
Number of pages7
JournalJournal of Immunology
Volume183
Issue number7
DOIs
Publication statusPublished - Oct 1 2009

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

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