From Allergy to Tumor Immunology: The Dual Role of Antigen-Specific IgE-Mechanisms, Challenges, and Prospects for Clinical Translation.

This review aims to systematically explore the dual role of antigen-specific IgE (AS-IgE) in allergic reactions and tumor immunity, focusing on the possibility, mechanism and current obstacles of its clinical transformation. Recent studies have revealed that AS-IgE is not only a single function of promoting allergies. It can activate antibody-dependent cytotoxicity (ADCC) and phagocytosis (ADCP) by binding to FcεRI receptors on the surface of immune cells (common in monocytes and macrophages), thereby reshaping the surrounding environment of tumors (TME) and enhancing the anticancer activity of CD8+ T cells. However, this duality also carries risks. For example, AS-IgE may induce the shift of Th2 immune response, causing immunosuppression and thus contributing to tumors. At the same time, the potential for it to activate allergic reactions remains a significant barrier to clinical application. It is worth noting that some experiments have tried to optimize AS-IgE through engineering modification. For example, sialic acid modification has been observed to reduce its sensitivity to allergic stimuli, providing ideas for safe applications. These findings suggest that AS-IgE is expected to become a new tool for tumor immunotherapy. However, in order to achieve transformation, it is necessary to first solve the key issues: how to balance its anti-cancer effect with allergies and tumor-promoting risks? At present, optimizing safety (especially reducing the risk of allergy) is the primary task, and exploring the combination with immune checkpoint inhibitors may improve the efficacy. Future research should be closer to the individual differences of patients, based on the characteristics of tumor environment in different people, and accurately regulate the dual role of AS-IgE. Only in this way can this molecule truly move from the laboratory to the clinic.