Clinical Utility of Basophil CD203c as a Biomarker for Predicting the Timing of Hypersensitivity Reaction in Carboplatin Rechallenge: Three Case Reports

Iwamoto, Takuya; Sugimoto, Hiroko; Tabata, Tsutomu; Okuda, Masahiro

doi:10.1016/j.clinthera.2016.04.034

Cited by 15 publications

(16 citation statements)

References 13 publications

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“…Next, we investigated whether the basophil activation test (BAT) can confirm previous hypersensitivity to a therapeutic agent in a cancer patient. In concordance with data from several case studies [ 5 , 6 , 26 , 27 , 28 , 29 ], clinical hypersensitivity to chemotherapy was reflected by activation following ex vivo basophil stimulation with these agents. In blood from a patient with ovarian cancer who had experienced a systemic reaction during intravenous (IV) infusion of paclitaxel over four years previously, ex vivo basophil activation was triggered following incubation with paclitaxel (2.5–25 μg/mL), to a degree comparable to that measured following stimulation with anti-IgE and fMLP ( Figure 3 C,E).…”

Section: Resultssupporting

confidence: 86%

“…Furthermore, in concordance with case studies of hypersensitivity to chemotherapies [ 5 , 6 , 26 , 27 , 28 , 29 ], we detected blood basophil activation by paclitaxel in a patient who had previously experienced systemic reaction to therapeutic paclitaxel IV infusion. In addition to activation by IgE-mediated and non-IgE mediated stimuli, basophil CD63 expression was also elevated following incubation with paclitaxel, but not with carboplatin, a chemotherapy that the patient was known to tolerate.…”

Section: Discussionsupporting

confidence: 86%

“…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. To date, however, 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 ]. Here, we conduct the first evaluation of basophils in a cohort of 53 ovarian cancer patients with diverse tumor histologies and treatment histories (treatment-naïve, chemotherapy, debulking surgery, targeted monoclonal antibodies (mAbs), small molecule inhibitors).…”

Section: Introductionmentioning

confidence: 99%

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Basophils from Cancer Patients Respond to Immune Stimuli and Predict Clinical Outcome

Bax

Chauhan

Stavraka

et al. 2020

Cells

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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.

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Section: Resultssupporting

confidence: 86%

Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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Basophils from Cancer Patients Respond to Immune Stimuli and Predict Clinical Outcome

Bax

Chauhan

Stavraka

et al. 2020

Cells

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“…49 Several markers up-regulated upon activation of basophils, such as CD203c, deserved interest as possible prognostic biomarker in non allergic immunotherapy, such as in carboplatin desensitization. 50 During allergen immunotherapy basophils themselves may be able to dampen allergy induced by the therapy, even apparently without an immune T cell-mediated surveillance. A possible mechanism is basophil anergy.…”

Section: Background On the Immune Regulatory Role Of Basophilsmentioning

confidence: 99%

The role of basophils as innate immune regulatory cells in allergy and immunotherapy

Chirumbolo

Bjørklund

Sboarina

et al. 2018

Human Vaccines & Immunotherapeutics

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Basophils are circulating cells that are associated quite exclusively with allergy response and hypersensitivity reactions but their role in the immune network might be much more intriguing and complex than previously expected. The feasibility of testing their biology in vitro for allergy research and diagnosis, due fundamentally to their quite easy availability in the peripheral blood, made them the major source for assessing allergy in the laboratory assay, when yet many further cells such as mast cells and eosinophils are much more involved as effector cells in allergy than circulating basophils. Interestingly, basophil numbers change rarely in peripheral blood during an atopic response, while we might yet observe an increase in eosinophils and modification in the biology of mast cells in the tissue during an hypersensitivity response. Furthermore, the fact that basophils are very scanty in numbers suggests that they should mainly serve as regulatory cells in immunity, rather than effector leukocytes, as still believed by the majority of physicians. In this review we will try to describe and elucidate the possible role of these cells, known as "innate IL4-producing cells" in the immune regulation of allergy and their function in allergen immunotherapy.

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“…BAT has also been studied as a possible diagnostic method, given the role of basophils and mast cells as key cells in immediate hypersensitivity reactions. Viardot-Helmer et al [15] found an increased expression of CD63 with exposure to cisplatin; Iwamoto et al [16][17][18] and Jean-Luc [19] detected increased expression of the CD203C marker after incubation with carboplatin and oxaliplatin, respectively; Giavina-Bianchi et al [20] evaluated CD63 and CD203c expression in patients submitted to rapid drug desensitization (RDD) with oxaliplatin and carboplatin, obtaining positive results in 73% of patients. Due to the existing limitations of skin tests, further studies are essential to ascertain the role of the in vitro diagnostic methods, particularly BAT, in hypersensitivity reactions to platinum compounds, as well as to make comparisons with controls in order to gain a better understanding of the underlying immunological mechanisms.…”

Section: Introductionmentioning

confidence: 99%

The Contribution of the Basophil Activation Test to the Diagnosis of Hypersensitivity Reactions to Oxaliplatin

Ornelas

Caiado

Melo

et al. 2018

Int Arch Allergy Immunol

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Cytostatics, mainly oxaliplatin, are widely used to treat oncological diseases. There has been an increase in hypersensitivity reactions to these drugs, mostly IgE-mediated. Skin tests are the main diagnostic method used but they may induce irritant local reactions and contamination by health care professionals. The main goals of this work were to evaluate the contribution of the basophil activation test (BAT) as a diagnostic tool for hypersensitivity reactions to oxaliplatin, and to compare the expression of CD63 and CD203c molecules. BAT was performed with oxaliplatin in 6 oncological patients with previous documented hypersensitivity reactions to oxaliplatin and in 5 controls (4 oncological patients tolerant to oxaliplatin and 1 healthy control), assessing CD63 and CD203c expression on basophil population. We found higher values for the basophil activation percentage and mean stimulation index for CD203c expression with all oxaliplatin concentrations tested (most significant at 150 μg/mL: p = 0,0087; p = 0.0222) in the patients than in controls. The same did not occur, with statistical significance, for CD63 expression. When we compared the 2 activation markers in the patients, we observed a more enhanced expression of CD203c in both evaluations, with statistical significance at the 150-μg/mL concentration (p = 0,026; p = 0,0129). These data show a higher positivity of BAT with oxaliplatin in patients with previous hypersensitivity reactions, when compared to controls, suggesting that BAT may be a promising diagnostic method as an alternative to skin tests. CD203c appears to play a more prominent role than CD63, which is consistent with what is published in the literature.

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Clinical Utility of Basophil CD203c as a Biomarker for Predicting the Timing of Hypersensitivity Reaction in Carboplatin Rechallenge: Three Case Reports

Cited by 15 publications

References 13 publications

Basophils from Cancer Patients Respond to Immune Stimuli and Predict Clinical Outcome

Basophils from Cancer Patients Respond to Immune Stimuli and Predict Clinical Outcome

The role of basophils as innate immune regulatory cells in allergy and immunotherapy

The Contribution of the Basophil Activation Test to the Diagnosis of Hypersensitivity Reactions to Oxaliplatin

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