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

Abstract

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.