Degranulation Cancer Immunotherapy: Harnessing the Allergy Cascade to Induce Tumor Apoptosis

Cancer immunotherapy has focused on adaptive T-cell–based strategies, such as checkpoint inhibitors and CAR-T cells. However, effector cells of the allergy cascade—basophils, eosinophils, mast cells, and neutrophils—remain underexplored as cytotoxic agents within the tumor microenvironment. These cells survive and function in nutrient-deprived tumors through metabolic reprogramming, a glycolytic switch (i.e., Warburg effect) which enables sustained activity despite hypoxia and glucose competition. Degranulation cancer immunotherapy (DCI) is proposed, in which forced atopy is induced to enrich tumor-resident effector cells with allergen-specific immunoglobulin. Then, intratumoral administration of the sensitizing allergen triggers targeted degranulation, releasing cytotoxic mediators, and inducing apoptosis of adjacent tumor cells. This review integrates immunometabolism, IgE biology, and tumor immunology to provide a mechanistic rationale, outlines a potential therapeutic protocol, and proposes frontier research directions. DCI may represent a low-cost, innate immunity–based alternative or complement to current immunotherapies, with applicability across a broad range of solid tumors.