Abstract
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.
Highlights
Despite their small numbers in circulating white blood cells, basophils can elicit powerful effector functions, playing a key role in allergies
We investigated the capacity of basophils from ovarian cancer patients to respond to established external IgE- and non-IgE-dependent activation and degranulation stimuli
We evaluated basophils from patients who had been previously treated with targeted anti-cancer therapies: (i) the anti-VEGF mAb bevacizumab [47,48,49] (n = 9), the only antibody approved for the treatment of ovarian cancer, and the administration of which has been reported to trigger hypersensitivity [48,49,50]; (ii) the poly-ADP ribose polymerase (PARP) inhibitors olaparib (n = 1) and niraparib [51,52,53] (n = 1); (iii) the anti-PD-L1 mAb avelumab [47] (n = 2)
Summary
Despite their small numbers in circulating white blood cells, basophils can elicit powerful effector functions, playing a key role in allergies. The basophil activation test (BAT) [8,9,10] is widely used to study and predict type 1 hypersensitivity reactions to food [11,12,13,14,15], venom [16,17,18] and drugs [19,20,21,22,23,24,25] in the allergy field. Its application to study basophils ex vivo in the context of cancer has been limited to case reports or small studies focused on the detection of allergic reactions to chemotherapeutic agents [5,6,26,27,28,29].
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