St. John's Institute of Dermatology, School of Basic & Medical Biosciences, King's College London, London SE1 9RT, UK.
School of Cancer & Pharmaceutical Sciences, King's College London, Guy's Hospital, London SE1 9RT, UK.
Cells. 2020 Jul 7;9(7):1631. doi: 10.3390/cells9071631.
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 ( = 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 ( = 35), and gene signatures indicating the presence of activated basophils in tumors ( = 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.
嗜碱性粒细胞参与过敏反应的表现,但目前对于其激活倾向及其在癌症患者中的预后价值仍不清楚。在健康人群和特应性个体中,在来自卵巢癌患者(=53)的血液中都鉴定到了具有不同肿瘤组织学和治疗史的嗜碱性粒细胞群体。通过使用嗜碱性粒细胞激活测试(BAT)测量 CD63 表达来评估嗜碱性粒细胞的体外激活情况。无论之前是否接受过治疗,嗜碱性粒细胞都可以通过 IgE(抗 FcεRI 和抗 IgE)和非 IgE(fMLP)介导的刺激来激活。嗜碱性粒细胞通过体外暴露于紫杉醇而被激活,但不会被其他抗癌疗法激活,这与紫杉醇全身性过敏反应的临床病史一致。蛋白和基因表达分析支持卵巢肿瘤中存在嗜碱性粒细胞(CCR3、CD123、FcεRI)和激活的嗜碱性粒细胞(CD63、CD203c、类胰蛋白酶)。循环嗜碱性粒细胞数量增加(=35)、体外刺激能力更强的细胞(=35),以及肿瘤中存在激活的嗜碱性粒细胞的基因特征(=439),均与卵巢癌患者的生存改善相关。癌症患者的循环嗜碱性粒细胞对 IgE 和非 IgE 介导的信号有反应,这可能有助于识别对治疗剂的过敏反应。激活的循环和肿瘤浸润嗜碱性粒细胞可能是肿瘤学中的潜在生物标志物。