IgG4 subclass antibodies impair antitumor immunity in melanoma

摘要: Host-induced antibodies and their contributions to cancer inflammation are largely unexplored. IgG4 subclass present in IL-10–driven Th2 immune responses some inflammatory conditions. Since Th2-biased is a hallmark of tumor microenvironments, we investigated the presence functional implications malignant melanoma. Consistent with inflammation, CD22+ B cells IgG4+-infiltrating accumulated tumors, IL-10, IL-4, tumor-reactive were expressed situ. When compared from patient lymph nodes blood, tumor-associated polarized produce IgG4. Secreted increased VEGF IgG4, enhanced IL-10 secretion cocultures. Unlike IgG1, an engineered antigen-specific was ineffective triggering effector cell–mediated killing vitro. Antigen-specific nonspecific inhibited IgG1-mediated tumoricidal functions. blockade mediated through reduction FcγRI activation. Additionally, significantly impaired potency IgG1 human melanoma xenograft mouse model. Furthermore, serum inversely correlated survival. These findings suggest that promoted by tumor-induced may restrict cell functions against providing previously unexplored aspect escape basis for biomarker development patient-specific therapeutic approaches.