Basophils in Immunity: Activation Pathways, Roles in Allergy and AllergoOncology and Application of the Basophil...

Basophils, the least abundant leukocytes, are increasingly recognised as potent immunomodulators. Upon activation, they rapidly release preformed granule-associated mediators including histamine and lipid mediators such as LTC₄, while cytokine production occurs over a longer timescale, contributing to downstream immune responses. Basophil activation is driven by IgE-dependent FcεRI crosslinking or IL-3, complement and Toll-like receptor (TLR) pathways, enabling diverse effector responses, including type I hypersensitivity to allergens. Through IL-4 and IL-13 secretion, basophils bridge innate and adaptive immunity, promoting Th2 differentiation, B cell activation and recruiting eosinophils. Beyond allergy, basophils contribute to inflammation, angiogenesis, cancer immune surveillance and tumour progression. Basophils participate in IgE-dependent type I hypersensitivity to small-molecule drugs, chemotherapeutics and monoclonal antibodies, becoming activated when drugs cross-link specific IgE-FcεRI complexes, driving rapid mediator release and amplifying Th2-skewed inflammation. The basophil activation test (BAT), which quantifies activation markers, such as CD63 and CD203c, provides an ex vivo functional measurement of these responses and serves as a biomarker of IgE-mediated hypersensitivity. In oncology, BAT is applied to predict and monitor hypersensitivity reactions, drug desensitisation and support IgE-based therapeutics development. Collectively, basophils are emerging as pivotal immune regulators and BAT presents a mechanistic, clinically-actionable tool for advancing precision medicine in AllergoOncology.