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Basophil activation test in cancer patient blood evaluating potential hypersensitivity to an anti-tumor IgE therapeutic candidate Keywords: basophils; BAT; IgE; MOv18; ovarian cancer EN basophils BAT IgE MOv18 ovarian cancer 1 5 5 07/29/20 20200801 NES 200801 To the Editor, Monoclonal anti-tumor IgG antibodies are used widely to treat malignancies. These include superior affinity of IgE for cognate Fc receptors and the presence in tumors of effector cell populations (eg, macrophages and mast cells) known to exert anti-tumor activities when activated by IgE. [Extracted from the article]

Basophils are involved in manifestations of hypersensitivity, however, the current understanding of their propensity for activation and their prognostic value in cancer patients remains unclear. As in healthy and atopic individuals, basophil populations were identified in blood from ovarian cancer patients (n = 53) with diverse tumor histologies and treatment histories. Ex vivo basophil activation was measured by CD63 expression using the basophil activation test (BAT). Irrespective of prior treatment, basophils could be activated by stimulation with IgE- (anti-FcεRI and anti-IgE) and non-IgE (fMLP) mediated triggers. Basophil activation was detected by ex vivo exposure to paclitaxel, but not to other anti-cancer therapies, in agreement with a clinical history of systemic hypersensitivity reactions to paclitaxel. Protein and gene expression analyses support the presence of basophils (CCR3, CD123, FcεRI) and activated basophils (CD63, CD203c, tryptase) in ovarian tumors. Greater numbers of circulating basophils, cells with greater capacity for ex vivo stimulation (n = 35), and gene signatures indicating the presence of activated basophils in tumors (n = 439) were each associated with improved survival in ovarian cancer. Circulating basophils in cancer patients respond to IgE- and non-IgE-mediated signals and could help identify hypersensitivity to therapeutic agents. Activated circulating and tumor-infiltrating basophils may be potential biomarkers in oncology. [ABSTRACT FROM AUTHOR]