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

Abstract

<jats:p>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.</jats:p>

Cancer Cells Resistance Shaping by Tumor Infiltrating Myeloid Cells

“…A direct anti-tumor effect of eosinophils in a melanoma mouse model was shown to be dependent on the presence of IL-33 in the TME [ 277 ]. High relative circulating basophils and activated infiltrated basophils were positively associated with improved outcome in melanoma or ovarian cancer patients and, according to several data, basopenia was associated with a poor prognosis in colorectal cancer [ 278 , 279 , 280 ].…”

Is There a Role for Basophils in Cancer?

“…In a recent study, Bax and co-workers examined the role of basophils in ovarian cancer patients (204). They found that higher percentage of circulating basophils from ovarian cancer patients was positively associated with improved overall survival.…”

“…It has long been known that human ( 127 – 131 ) and mouse ( 62 , 73 , 124 – 126 ) basophils have a propensity to migrate from peripheral blood into sites of inflammation. Moreover, basophils were identified in human lung ( 50 ), gastric ( 127 , 128 ), pancreatic ( 11 , 91 ) and ovarian cancer ( 204 ). It was recently shown, at least in mice, that basophils are present in all phases of lung development ( 44 ), and display a divergent phenotype from peripheral blood.…”

“…In conclusion, the last years have witnessed exceptional progress in our understanding of basophil biology. Recent studies have demonstrated that basophils are present in the immune landscape of human ( 50 , 91 , 204 ) and experimental ( 62 , 91 ) tumors, play a role in lung development and M2 macrophage polarization ( 44 ), and participate in canonical ( 57 , 105 , 106 , 145 ) and non-canonical angiogenesis ( 151 ), and release BETs ( 117 , 118 ). Further investigations are required before we unravel the mysterious role of basophils in experimental cancer and, more importantly, in humans.…”

IgE Antibodies against Cancer: Efficacy and Safety

“…Furthermore, patients with cancer may develop antitumour IgE: greater numbers of IgE-expressing cells have been observed in head and neck tumours compared to normal mucosa [ 6 ] and an IgE derived from pancreatic cancer patients showed antitumoural activity in vitro [ 7 ]. Furthermore, it has recently been reported that FcεRI expression [ 8 ] and greater numbers of eosinophils and basophils, key IgE receptor (FcεR)-expressing effector cells [ 9 , 10 , 11 ], may be associated with improved outcomes for cancer patients. In mice, where it should be noted the human IgE system is not fully recapitulated and expression of the high-affinity IgE receptor (FcεRI) is only present in mast cells and basophils, a carcinogen-induced IgE response was protective against carcinogenesis [ 12 ], but conversely an inflammation-driven polyclonal IgE response promoted tumour outgrowth [ 13 ].…”