TY - JOUR
T1 - Antitumor IgE adjuvanticity
T2 - Key role of FcεRI
AU - Nigro, Elisa A.
AU - Brini, Anna T.
AU - Soprana, Elisa
AU - Ambrosi, Alessandro
AU - Dombrowicz, David
AU - Siccardi, Antonio G.
AU - Vangelista, Luca
PY - 2009/10/1
Y1 - 2009/10/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.0900842
DO - 10.4049/jimmunol.0900842
M3 - Article
C2 - 19748979
AN - SCOPUS:70449732758
VL - 183
SP - 4530
EP - 4536
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 7
ER -