Antitumor IgE Adjuvanticity: Key Role of FcεRI

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.

Cutting Edge: IgE Plays an Active Role in Tumor Immunosurveillance in Mice

“…We challenged both IgE-KO and matching wild-type (WT) mice by s.c. injection of TS/A tumor cells. After tumor cell engraftment, tumor volume progression in WT mice was comparable to that reported in a previous study (11) and identical to that observed in IgE-KO mice (Fig. 1A).…”

“…To account for the dependence among longitudinal observations as well as for possible undetectable initial differences, tumor growth curves were estimated by an exponential mixed effect model with multiplicative errors: V(t) = a 0 e ait e, where V is the volume of the tumor at time t, e has log-normal distribution, and i is the experimental condition (11). The model was fitted by restricted maximum likelihood (19).…”

“…We previously established that the adjuvant effect of IgE in tumor vaccination is dependent on FceRI and not on CD23 (11). Thus, we tested whether also endogenous IgE relies on the IgE-FceRI axis to exert antitumor effects.…”

“…In the N2C model, mice were challenged s.c. with 6 3 10 5 tumor cells. Tumor growth was monitored at 1-to 3-d intervals by measuring tumor volume with a caliper as already described (11,12). Animals were euthanized when the tumors became .500 mm 3 .…”

“…The redirection of the potent IgE-driven immune activation to induce tumor rejection is a strategy that has been adopted by several research groups with different approaches, either by passive or active immunotherapy (8,9). When provided exogenously, we have previously documented that IgE is a potent adjuvant of antitumor vaccination in mice (10)(11)(12). This discovery prompted us to this work in which we explore endogenous IgE in tumor immunosurveillance, with the aim of defining a new important role for the evolution of the IgE isotype.…”