These findings are consistent with our previous studies in which we demonstrated a shift towards an immunoactive TME with IgE immunotherapy in melanoma and ovarian cancer contexts.15 16 Aside from immunomodulatory effects, Tras IgE treatment in these medium HER2-expressing, Tras-resistant tumors also led to a downregulation of pathways directly associated with tumorigenesis, such as blood vessel development44 and Wnt signalling,45 pointing to the impact of IgE-mediated immunomodulation against cancer-promoting mechanisms. This evidence concerns the gene ERBB2 and melanoma.